FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Biochemistry2017; 56(28); 3632-3646; doi: 10.1021/acs.biochem.7b00446

Horse Liver Alcohol Dehydrogenase: Zinc Coordination and Catalysis.

Abstract: During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism might involve a pentacoordinated zinc or a double-displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1, and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. The apoenzyme and its complex with adenosine 5'-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174, and a water molecule. The bidentate chelators 2,2'-bipyridine and 1,10-phenanthroline displace the water and form a pentacoordinated zinc. The enzyme-NADH complex has a closed conformation similar to that of ternary complexes with coenzyme and substrate analogues; the coordination of the catalytic zinc is similar to that found in the apoenzyme, except that a minor, alternative position for the catalytic zinc is ∼1.3 Å from the major position and closer to Glu-68, which could form the alternative coordination to the catalytic zinc. Complexes with NADH and N-1-methylhexylformamide or N-benzylformamide (or with NAD and fluoro alcohols) have the classical tetracoordinated zinc, and no water is bound to the zinc or the nicotinamide rings. The major forms of the enzyme in the mechanism have a tetracoordinated zinc, where the carboxylate group of Glu-68 could participate in the exchange of water and substrates on the zinc. Hydride transfer in the Michaelis complexes does not involve a nearby water.
Get Full Text
Publication Date: 2017-07-07 PubMed ID: 28640600PubMed Central: PMC5518280DOI: 10.1021/acs.biochem.7b00446Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explores how catalysis occurs in liver alcohol dehydrogenase (ADH), an enzyme found in horses, focusing on the role of water and zinc’s coordination in the process. The researchers used X-ray crystallography to observe changes in the enzyme and its complexes.

Methodology and Findings

  • The researchers studied the enzyme’s function and configuration through X-ray crystallography. This technique allowed them to monitor the structural changes in the enzyme and its complexes at a molecular level.
  • When observing the apoenzyme (a form of the enzyme without its required cofactors) ADH, and when it combined with adenosine 5′-diphosphoribose, the researchers noted an open protein conformation. They found the catalytic zinc to be in one position, tetracoordinated (bonded with four ligands), with the amino acids Cys-46, His-67, Cys-174, and one water molecule.
  • Interaction with 2,2′-bipyridine and 1,10-phenanthroline chelators resulted in the displacement of water and formation of pentacoordinated zinc (five points of attachment).

Complex Conformations and Participation of Zinc

  • For the enzyme-NADH complex, the conformation resembled that of ternary complexes with coenzymes and substrate analogues. The coordination of catalytic zinc was similar to the apoenzyme, with a minor position found closer to the Glu-68 residue.
  • Complexes with NADH and N-1-methylhexylformamide or N-benzylformamide (or with NAD and fluoro alcohols) exhibited a tetracoordinated zinc. In these configurations, no water was observed to bind to the zinc or the nicotinamide rings.
  • The predominant forms of the enzyme in the mechanism have a tetracoordinated zinc, where the carboxylic group from Glu-68 could possibly participate in substrate and water exchange on the zinc.

Conclusion

  • The research proposes that mechanism of hydride transfer in the Michaelis complexes (an enzyme-substrate complex) doesn’t involve any proximate water.
  • The detailed study of these enzyme complexes provides a greater understanding of the ADH catalyzing process. Further research could aid in development of biochemical models and pharmaceutical advancements.

Cite This Article

APA
Plapp BV, Savarimuthu BR, Ferraro DJ, Rubach JK, Brown EN, Ramaswamy S. (2017). Horse Liver Alcohol Dehydrogenase: Zinc Coordination and Catalysis. Biochemistry, 56(28), 3632-3646. https://doi.org/10.1021/acs.biochem.7b00446

Publication

Biochemistry
ISSN: 1520-4995
NlmUniqueID: 0370623
Country: United States
Language: English
Volume: 56
Issue: 28
Pages: 3632-3646

Researcher Affiliations

Plapp, Bryce V
  • Department of Biochemistry, The University of Iowa , Iowa City, Iowa 52242, United States.
Savarimuthu, Baskar Raj
  • Department of Biochemistry, The University of Iowa , Iowa City, Iowa 52242, United States.
Ferraro, Daniel J
  • Department of Biochemistry, The University of Iowa , Iowa City, Iowa 52242, United States.
Rubach, Jon K
  • Department of Biochemistry, The University of Iowa , Iowa City, Iowa 52242, United States.
Brown, Eric N
  • Department of Biochemistry, The University of Iowa , Iowa City, Iowa 52242, United States.
Ramaswamy, S
  • Department of Biochemistry, The University of Iowa , Iowa City, Iowa 52242, United States.

MeSH Terms

  • 2,2'-Dipyridyl / metabolism
  • Adenosine Diphosphate Ribose / metabolism
  • Alcohol Dehydrogenase / chemistry
  • Alcohol Dehydrogenase / metabolism
  • Animals
  • Catalytic Domain
  • Crystallography, X-Ray
  • Formamides / metabolism
  • Horses
  • Kinetics
  • Liver / enzymology
  • Liver / metabolism
  • Models, Molecular
  • NAD / metabolism
  • Phenanthrolines / metabolism
  • Protein Binding
  • Protein Conformation
  • Water / chemistry
  • Water / metabolism
  • Zinc / chemistry
  • Zinc / metabolism

Grant Funding

  • T32 GM007337 / NIGMS NIH HHS
  • R01 AA000279 / NIAAA NIH HHS
  • T32 GM008365 / NIGMS NIH HHS

Conflict of Interest Statement

The authors declare no competing financial interest.

References

This article includes 104 references
  1. Sekhar VC, Plapp BV. Rate constants for a mechanism including intermediates in the interconversion of ternary complexes by horse liver alcohol dehydrogenase.. Biochemistry 1990 May 8;29(18):4289-95.
    doi: 10.1021/bi00470a005pubmed: 2161681google scholar: lookup
  2. Kovaleva EG, Plapp BV. Deprotonation of the horse liver alcohol dehydrogenase-NAD+ complex controls formation of the ternary complexes.. Biochemistry 2005 Sep 27;44(38):12797-808.
    doi: 10.1021/bi050865vpubmed: 16171395google scholar: lookup
  3. Plapp BV. Conformational changes and catalysis by alcohol dehydrogenase.. Arch Biochem Biophys 2010 Jan 1;493(1):3-12.
    doi: 10.1016/j.abb.2009.07.001pmc: PMC2812590pubmed: 19583966google scholar: lookup
  4. Eklund H, Nordström B, Zeppezauer E, Söderlund G, Ohlsson I, Boiwe T, Söderberg BO, Tapia O, Brändén CI, Akeson A. Three-dimensional structure of horse liver alcohol dehydrogenase at 2-4 A resolution.. J Mol Biol 1976 Mar 25;102(1):27-59.
    doi: 10.1016/0022-2836(76)90072-3pubmed: 178875google scholar: lookup
  5. Eklund H, Samma JP, Wallén L, Brändén CI, Akeson A, Jones TA. Structure of a triclinic ternary complex of horse liver alcohol dehydrogenase at 2.9 A resolution.. J Mol Biol 1981 Mar 15;146(4):561-87.
    doi: 10.1016/0022-2836(81)90047-4pubmed: 7024556google scholar: lookup
  6. Brändén C.-I., Jörnvall H., Eklund H., Furugren B.. Alcohol Dehydrogenases. The Enzymes, 3rd ed., Vol. 11, pp 103–190, Elsevier, Amsterdam.
  7. Eklund H., Brändén C. I.. Alcohol Dehydrogenase. In Biological Macromolecules and Assemblies: Vol. 3-Active Sites of Enzymes (Jurnak F. A., and McPherson A., Eds.) pp 73–141, Wiley, New York.
  8. Plapp BV, Ramaswamy S. Atomic-resolution structures of horse liver alcohol dehydrogenase with NAD(+) and fluoroalcohols define strained Michaelis complexes.. Biochemistry 2012 May 15;51(19):4035-48.
    doi: 10.1021/bi300378npmc: PMC3352959pubmed: 22531044google scholar: lookup
  9. LeBrun LA, Park DH, Ramaswamy S, Plapp BV. Participation of histidine-51 in catalysis by horse liver alcohol dehydrogenase.. Biochemistry 2004 Mar 23;43(11):3014-26.
    doi: 10.1021/bi036103mpubmed: 15023053google scholar: lookup
  10. Al-Karadaghi S, Cedergren-Zeppezauer ES, Hövmoller S. Refined crystal structure of liver alcohol dehydrogenase-NADH complex at 1.8 A resolution.. Acta Crystallogr D Biol Crystallogr 1994 Nov 1;50(Pt 6):793-807.
    doi: 10.1107/S0907444994005263pubmed: 15299346google scholar: lookup
  11. Venkataramaiah TH, Plapp BV. Formamides mimic aldehydes and inhibit liver alcohol dehydrogenases and ethanol metabolism.. J Biol Chem 2003 Sep 19;278(38):36699-706.
    doi: 10.1074/jbc.M305419200pubmed: 12855684google scholar: lookup
  12. Cho H, Ramaswamy S, Plapp BV. Flexibility of liver alcohol dehydrogenase in stereoselective binding of 3-butylthiolane 1-oxides.. Biochemistry 1997 Jan 14;36(2):382-9.
    doi: 10.1021/bi9624604pubmed: 9003191google scholar: lookup
  13. Ramaswamy S, Scholze M, Plapp BV. Binding of formamides to liver alcohol dehydrogenase.. Biochemistry 1997 Mar 25;36(12):3522-7.
    doi: 10.1021/bi962491zpubmed: 9132002google scholar: lookup
  14. Dworschack RT, Plapp BV. pH, isotope, and substituent effects on the interconversion of aromatic substrates catalyzed by hydroxybutyrimidylated liver alcohol dehydrogenase.. Biochemistry 1977 Jun 14;16(12):2716-25.
    doi: 10.1021/bi00631a020pubmed: 19037google scholar: lookup
  15. VALLEE BL, COOMBS TL. Complex formation of 1,10-phenanthroline with zinc ions and the zinc of alcohol dehydrogenase of horse liver.. J Biol Chem 1959 Oct;234:2615-20.
    pubmed: 13840891
  16. VALLEE BL, WILLIAMS RJ, HOCH FL. The role of zinc in alcohol dehydrogenase. IV. The kinetics of the instantaneous inhibition of horse liver alcohol dehydrogenase by 1,10-phenanthroline.. J Biol Chem 1959 Oct;234:2621-6.
    pubmed: 13840894
  17. DeTraglia MC, Schmidt J, Dunn MF, McFarland JT. Liver alcohol dehydrogenase-coenzyme reaction rates.. J Biol Chem 1977 May 25;252(10):3493-500.
    pubmed: 16905
  18. Boiwe T, Bränden CI. X-ray investigation of the binding of 1,10-phenanthroline and imidazole to horse-liver alcohol dehydrogenase.. Eur J Biochem 1977 Jul 1;77(1):173-9.
    doi: 10.1111/j.1432-1033.1977.tb11655.xpubmed: 561693google scholar: lookup
  19. Frolich M, Creighton DJ, Sigman DS. Limiting rates of ligand association to alcohol dehydrogenase.. Arch Biochem Biophys 1978 Aug;189(2):471-80.
    doi: 10.1016/0003-9861(78)90236-9pubmed: 213026google scholar: lookup
  20. Evans SA, Shore JD. The role of zinc-bound water in liver alcohol dehydrogenase catalysis.. J Biol Chem 1980 Feb 25;255(4):1509-14.
    pubmed: 6986372
  21. Eklund H, Plapp BV, Samama JP, Brändén CI. Binding of substrate in a ternary complex of horse liver alcohol dehydrogenase.. J Biol Chem 1982 Dec 10;257(23):14349-58.
    pubmed: 6754727
  22. Meijers R, Morris RJ, Adolph HW, Merli A, Lamzin VS, Cedergren-Zeppezauer ES. On the enzymatic activation of NADH.. J Biol Chem 2001 Mar 23;276(12):9316-21.
    doi: 10.1074/jbc.M010870200pubmed: 11134046google scholar: lookup
  23. Meijers R, Adolph HW, Dauter Z, Wilson KS, Lamzin VS, Cedergren-Zeppezauer ES. Structural evidence for a ligand coordination switch in liver alcohol dehydrogenase.. Biochemistry 2007 May 8;46(18):5446-54.
    doi: 10.1021/bi6023594pubmed: 17429946google scholar: lookup
  24. Makinen MW, Yim MB. Coordination environment of the active-site metal ion of liver alcohol dehydrogenase.. Proc Natl Acad Sci U S A 1981 Oct;78(10):6221-5.
    doi: 10.1073/pnas.78.10.6221pmc: PMC349010pubmed: 6273859google scholar: lookup
  25. Makinen MW, Maret W, Yim MB. Neutral metal-bound water is the base catalyst in liver alcohol dehydrogenase.. Proc Natl Acad Sci U S A 1983 May;80(9):2584-8.
    doi: 10.1073/pnas.80.9.2584pmc: PMC393870pubmed: 6302696google scholar: lookup
  26. Werth M. T., Tang S.-F., Formicka G., Zeppezauer M., Johnson M. K.. Magnetic circular dichroism and electron paramagnetic resonance studies of cobalt-substituted horse liver alcohol dehydrogenase. Inorg. Chem. 34, 218–228.
    doi: 10.1021/ic00105a037google scholar: lookup
  27. Andersson I., Bauer R., Demeter I.. Structural information concerning the catalytic metal site in horse liver alcohol-dehydrogenase, obtained by perturbed angular-correlation spectroscopy on Cd-111. Inorg. Chim. Acta 67, 53–59.
    doi: 10.1016/S0020-1693(00)85039-2google scholar: lookup
  28. Hemmingsen L, Bauer R, Bjerrum MJ, Zeppezauer M, Adolph HW, Formicka G, Cedergren-Zeppezauer E. Cd-substituted horse liver alcohol dehydrogenase: catalytic site metal coordination geometry and protein conformation.. Biochemistry 1995 May 30;34(21):7145-53.
    doi: 10.1021/bi00021a028pubmed: 7766625google scholar: lookup
  29. Hemmingsen L, Bauer R, Bjerrum MJ, Adolph HW, Zeppezauer M, Cedergren-Zeppezauer E. The protein conformation of Cd-substituted horse liver alcohol dehydrogenase and its metal-site coordination geometry in binary and ternary inhibitor complexes.. Eur J Biochem 1996 Oct 15;241(2):546-51.
    doi: 10.1111/j.1432-1033.1996.00546.xpubmed: 8917454google scholar: lookup
  30. Ryde U., Hemmingsen L.. The active-site metal coordination geometry of cadmium-substituted alcohol dehydrogenase - A theoretical interpretation of perturbed angular correlation of gamma-ray measurements. JBIC, J. Biol. Inorg. Chem. 2, 567–579.
    doi: 10.1007/s007750050171google scholar: lookup
  31. Kleifeld O, Frenkel A, Martin JM, Sagi I. Active site electronic structure and dynamics during metalloenzyme catalysis.. Nat Struct Biol 2003 Feb;10(2):98-103.
    doi: 10.1038/nsb889pubmed: 12524531google scholar: lookup
  32. Kleifeld O, Frenkel A, Bogin O, Eisenstein M, Brumfeld V, Burstein Y, Sagi I. Spectroscopic studies of inhibited alcohol dehydrogenase from Thermoanaerobacter brockii: proposed structure for the catalytic intermediate state.. Biochemistry 2000 Jul 4;39(26):7702-11.
    doi: 10.1021/bi0002030pubmed: 10869175google scholar: lookup
  33. Yang ZN, Bosron WF, Hurley TD. Structure of human chi chi alcohol dehydrogenase: a glutathione-dependent formaldehyde dehydrogenase.. J Mol Biol 1997 Jan 24;265(3):330-43.
    doi: 10.1006/jmbi.1996.0731pubmed: 9018047google scholar: lookup
  34. Sanghani PC, Robinson H, Bosron WF, Hurley TD. Human glutathione-dependent formaldehyde dehydrogenase. Structures of apo, binary, and inhibitory ternary complexes.. Biochemistry 2002 Sep 3;41(35):10778-86.
    doi: 10.1021/bi0257639pubmed: 12196016google scholar: lookup
  35. Sanghani PC, Bosron WF, Hurley TD. Human glutathione-dependent formaldehyde dehydrogenase. Structural changes associated with ternary complex formation.. Biochemistry 2002 Dec 24;41(51):15189-94.
    doi: 10.1021/bi026705qpubmed: 12484756google scholar: lookup
  36. Sanghani PC, Davis WI, Zhai L, Robinson H. Structure-function relationships in human glutathione-dependent formaldehyde dehydrogenase. Role of Glu-67 and Arg-368 in the catalytic mechanism.. Biochemistry 2006 Apr 18;45(15):4819-30.
    doi: 10.1021/bi052554qpubmed: 16605250google scholar: lookup
  37. Thomas LM, Harper AR, Miner WA, Ajufo HO, Branscum KM, Kao L, Sims PA. Structure of Escherichia coli AdhP (ethanol-inducible dehydrogenase) with bound NAD.. Acta Crystallogr Sect F Struct Biol Cryst Commun 2013 Jul;69(Pt 7):730-2.
    doi: 10.1107/S1744309113015170pmc: PMC3702314pubmed: 23832197google scholar: lookup
  38. Karlsson A, El-Ahmad M, Johansson K, Shafqat J, Jörnvall H, Eklund H, Ramaswamy S. Tetrameric NAD-dependent alcohol dehydrogenase.. Chem Biol Interact 2003 Feb 1;143-144:239-45.
    doi: 10.1016/S0009-2797(02)00222-3pubmed: 12604209google scholar: lookup
  39. Raj SB, Ramaswamy S, Plapp BV. Yeast alcohol dehydrogenase structure and catalysis.. Biochemistry 2014 Sep 16;53(36):5791-803.
    doi: 10.1021/bi5006442pmc: PMC4165444pubmed: 25157460google scholar: lookup
  40. Plapp BV, Charlier HA Jr, Ramaswamy S. Mechanistic implications from structures of yeast alcohol dehydrogenase complexed with coenzyme and an alcohol.. Arch Biochem Biophys 2016 Feb 1;591:35-42.
    doi: 10.1016/j.abb.2015.12.009pubmed: 26743849google scholar: lookup
  41. Esposito L, Sica F, Raia CA, Giordano A, Rossi M, Mazzarella L, Zagari A. Crystal structure of the alcohol dehydrogenase from the hyperthermophilic archaeon Sulfolobus solfataricus at 1.85 A resolution.. J Mol Biol 2002 Apr 26;318(2):463-77.
    doi: 10.1016/S0022-2836(02)00088-8pubmed: 12051852google scholar: lookup
  42. Esposito L, Bruno I, Sica F, Raia CA, Giordano A, Rossi M, Mazzarella L, Zagari A. Structural study of a single-point mutant of Sulfolobus solfataricus alcohol dehydrogenase with enhanced activity.. FEBS Lett 2003 Mar 27;539(1-3):14-8.
    doi: 10.1016/S0014-5793(03)00173-Xpubmed: 12650918google scholar: lookup
  43. Ganzhorn AJ, Plapp BV. Carboxyl groups near the active site zinc contribute to catalysis in yeast alcohol dehydrogenase.. J Biol Chem 1988 Apr 15;263(11):5446-54.
    pubmed: 3281940
  44. Ryde U. On the role of Glu-68 in alcohol dehydrogenase.. Protein Sci 1995 Jun;4(6):1124-32.
    doi: 10.1002/pro.5560040611pmc: PMC2143135pubmed: 7549877google scholar: lookup
  45. Plapp BV, Eklund H, Brändén CI. Crystallography of liver alcohol dehydrogenase complexed with substrates.. J Mol Biol 1978 Jun 15;122(1):23-32.
    doi: 10.1016/0022-2836(78)90105-5pubmed: 209195google scholar: lookup
  46. Abdallah MA, Biellmann JF, Nordström B, Brändén CI. The conformation of adenosine diphosphoribose and 8-bromoadenosine diphosphoribose when bound to liver alcohol dehydrogenase.. Eur J Biochem 1975 Jan 15;50(3):475-81.
    doi: 10.1111/j.1432-1033.1975.tb09885.xpubmed: 163741google scholar: lookup
  47. Gibbons BJ, Hurley TD. Structure of three class I human alcohol dehydrogenases complexed with isoenzyme specific formamide inhibitors.. Biochemistry 2004 Oct 5;43(39):12555-62.
    doi: 10.1021/bi0489107pubmed: 15449945google scholar: lookup
  48. Zeppezauer E., Söderberg B.-O., Brändén C.-I., Åkeson Å., Theorell H.. Crystallization of horse liver alcohol dehydrogenase complexes from alcohol solutions. Acta Chem. Scand. 21, 1099–1101.
    doi: 10.3891/acta.chem.scand.21-1099google scholar: lookup
  49. Plapp BV. Enhancement of the activity of horse liver alcohol dehydrogenase by modification of amino groups at the active sites.. J Biol Chem 1970 Apr 10;245(7):1727-35.
    pubmed: 4314596
  50. YONETANI T, THEORELL H. STUDIES ON LIVER ALCOHOL HYDROGENASE COMPLEXES. 3. MULTIPLE INHIBITION KINETICS IN THE PRESENCE OF TWO COMPETITIVE INHIBITORS.. Arch Biochem Biophys 1964 Jul 20;106:243-51.
    doi: 10.1016/0003-9861(64)90184-5pubmed: 14217165google scholar: lookup
  51. Schindler JF, Berst KB, Plapp BV. Inhibition of human alcohol dehydrogenases by formamides.. J Med Chem 1998 May 7;41(10):1696-701.
    doi: 10.1021/jm9707380pubmed: 9572895google scholar: lookup
  52. Pflugrath JW. The finer things in X-ray diffraction data collection.. Acta Crystallogr D Biol Crystallogr 1999 Oct;55(Pt 10):1718-25.
    doi: 10.1107/S090744499900935Xpubmed: 10531521google scholar: lookup
  53. Kabsch W. XDS.. Acta Crystallogr D Biol Crystallogr 2010 Feb;66(Pt 2):125-32.
    doi: 10.1107/S0907444909047337pmc: PMC2815665pubmed: 20124692google scholar: lookup
  54. Winn MD, Ballard CC, Cowtan KD, Dodson EJ, Emsley P, Evans PR, Keegan RM, Krissinel EB, Leslie AG, McCoy A, McNicholas SJ, Murshudov GN, Pannu NS, Potterton EA, Powell HR, Read RJ, Vagin A, Wilson KS. Overview of the CCP4 suite and current developments.. Acta Crystallogr D Biol Crystallogr 2011 Apr;67(Pt 4):235-42.
    doi: 10.1107/S0907444910045749pmc: PMC3069738pubmed: 21460441google scholar: lookup
  55. Jones TA, Zou JY, Cowan SW, Kjeldgaard M. Improved methods for building protein models in electron density maps and the location of errors in these models.. Acta Crystallogr A 1991 Mar 1;47 ( Pt 2):110-9.
    doi: 10.1107/S0108767390010224pubmed: 2025413google scholar: lookup
  56. Sheldrick GM. Crystal structure refinement with SHELXL.. Acta Crystallogr C Struct Chem 2015 Jan;71(Pt 1):3-8.
    doi: 10.1107/S2053229614024218pmc: PMC4294323pubmed: 25567568google scholar: lookup
  57. Chen VB, Arendall WB 3rd, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, Murray LW, Richardson JS, Richardson DC. MolProbity: all-atom structure validation for macromolecular crystallography.. Acta Crystallogr D Biol Crystallogr 2010 Jan;66(Pt 1):12-21.
    doi: 10.1107/S0907444909042073pmc: PMC2803126pubmed: 20057044google scholar: lookup
  58. Harris M, Jones TA. Molray--a web interface between O and the POV-Ray ray tracer.. Acta Crystallogr D Biol Crystallogr 2001 Aug;57(Pt 8):1201-3.
    doi: 10.1107/S0907444901007697pubmed: 11468417google scholar: lookup
  59. Kim K, Plapp BV. Inversion of substrate stereoselectivity of horse liver alcohol dehydrogenase by substitutions of Ser-48 and Phe-93.. Chem Biol Interact 2017 Oct 1;276:77-87.
    doi: 10.1016/j.cbi.2016.12.016pmc: PMC5481492pubmed: 28025168google scholar: lookup
  60. Bignetti E, Rossi GL, Zeppezauer E. Microspectrophotometric measurements on single crystals of coenzyme containing complexes of horse liver alcohol dehydrogenase.. FEBS Lett 1979 Apr 1;100(1):17-22.
    doi: 10.1016/0014-5793(79)81122-9pubmed: 220086google scholar: lookup
  61. Shearer GL, Kim K, Lee KM, Wang CK, Plapp BV. Alternative pathways and reactions of benzyl alcohol and benzaldehyde with horse liver alcohol dehydrogenase.. Biochemistry 1993 Oct 19;32(41):11186-94.
    doi: 10.1021/bi00092a031pubmed: 8218182google scholar: lookup
  62. Yahashiri A, Rubach JK, Plapp BV. Effects of cavities at the nicotinamide binding site of liver alcohol dehydrogenase on structure, dynamics and catalysis.. Biochemistry 2014 Feb 11;53(5):881-94.
    doi: 10.1021/bi401583fpmc: PMC3969020pubmed: 24437493google scholar: lookup
  63. Rubach JK, Plapp BV. Amino acid residues in the nicotinamide binding site contribute to catalysis by horse liver alcohol dehydrogenase.. Biochemistry 2003 Mar 18;42(10):2907-15.
    doi: 10.1021/bi0272656pubmed: 12627956google scholar: lookup
  64. Webb S. P., Agarwal P. K., Hammes-Schiffer S.. Combining electronic structure methods with the calculation of hydrogen vibrational wavefunctions: Application to hydride transfer in liver alcohol dehydrogenase. J. Phys. Chem. B 104, 8884–8894.
    doi: 10.1021/jp001635ngoogle scholar: lookup
  65. Billeter SR, Webb SP, Agarwal PK, Iordanov T, Hammes-Schiffer S. Hydride transfer in liver alcohol dehydrogenase: quantum dynamics, kinetic isotope effects, and role of enzyme motion.. J Am Chem Soc 2001 Nov 14;123(45):11262-72.
    doi: 10.1021/ja011384bpubmed: 11697969google scholar: lookup
  66. Luo J, Bruice TC. Dynamic structures of horse liver alcohol dehydrogenase (HLADH): results of molecular dynamics simulations of HLADH-NAD(+)-PhCH(2)OH, HLADH-NAD(+)-PhCH(2)O(-), and HLADH-NADH-PhCHO.. J Am Chem Soc 2001 Dec 5;123(48):11952-9.
    doi: 10.1021/ja0109747pubmed: 11724603google scholar: lookup
  67. Almarsson Ö., Bruice T. C.. Evaluation of the factors influencing reactivity and stereospecificity in NAD(P)H dependent dehydrogenase enzymes. J. Am. Chem. Soc. 115, 2125–2138.
    doi: 10.1021/ja00059a005google scholar: lookup
  68. Harding MM. Geometry of metal-ligand interactions in proteins.. Acta Crystallogr D Biol Crystallogr 2001 Mar;57(Pt 3):401-11.
    doi: 10.1107/S0907444900019168pubmed: 11223517google scholar: lookup
  69. Shore JD, Gutfreund H, Brooks RL, Santiago D, Santiago P. Proton equilibria and kinetics in the liver alcohol dehydrogenase reaction mechanism.. Biochemistry 1974 Sep 24;13(20):4185-91.
    doi: 10.1021/bi00717a019pubmed: 4370301google scholar: lookup
  70. Kvassman J, Pettersson G. Effect of pH on coenzyme binding to liver alcohol dehydrogenase.. Eur J Biochem 1979 Oct;100(1):115-23.
    doi: 10.1111/j.1432-1033.1979.tb02039.xpubmed: 39751google scholar: lookup
  71. Pettersson G. Liver alcohol dehydrogenase.. CRC Crit Rev Biochem 1987;21(4):349-89.
    doi: 10.3109/10409238609113616pubmed: 3304836google scholar: lookup
  72. Andersson P, Kvassman J, Lindström A, Oldén B, Pettersson G. Effect of NADH on the pKa of zinc-bound water in liver alcohol dehydrogenase.. Eur J Biochem 1981 Jan;113(3):425-33.
    doi: 10.1111/j.1432-1033.1981.tb05082.xpubmed: 7011796google scholar: lookup
  73. Oppenheimer NJ, Kaplan NO. Structure of the primary acid rearrangement product of reduced nicotinamide adenine dinucleotide (NADH).. Biochemistry 1974 Nov 5;13(23):4675-85.
    doi: 10.1021/bi00720a001pubmed: 4371814google scholar: lookup
  74. Oppenheimer N. J.. Chemical stabilty and reactivity of pyridine nucleotide coenzymes. In Pyridine Nucleotide Coenzymes. Chemical, Biochemical, and Medical Aspects, Part A (Dolphin D., Poulson R., and Avramović O., Eds.) pp 323–365, John Wiley, New York.
  75. Oppenheimer NJ, Kaplan NO. Glyceraldehyde-3-phosphate dehydrogenase catalyzed hydration of the 5-6 double bond of reduced beta-nicotinamide adenine dinucleotide (betaNADH). Formation of beta-6-hydroxy-1,4,5,6-tetrahydronicotinamide adenine dinucleotide.. Biochemistry 1974 Nov 5;13(23):4685-94.
    doi: 10.1021/bi00720a002pubmed: 4371815google scholar: lookup
  76. Alhambra C., Corchado J., Sánchez M. L., Garcia-Viloca M., Gao J., Truhlar D. G.. Canonical variational theory for enzyme kinetics with the protein mean force and multidimensional quantum mechanical tunneling dynamics. Theory and application to liver alcohol dehydrogenase. J. Phys. Chem. B 105, 11326–11340.
    doi: 10.1021/jp0120312google scholar: lookup
  77. Villà J., Warshel A.. Energetics and dynamics of enzymatic reactions. J. Phys. Chem. B 105, 7887–7907.
    doi: 10.1021/jp011048hgoogle scholar: lookup
  78. Cui Q., Elstner M., Karplus M.. A theoretical analysis of the proton and hydride transfer in liver alcohol dehydrogenase (LADH). J. Phys. Chem. B 106, 2721–2740.
    doi: 10.1021/jp013012vgoogle scholar: lookup
  79. Schneider G, Eklund H, Cedergren-Zeppezauer E, Zeppezauer M. Crystal structures of the active site in specifically metal-depleted and cobalt-substituted horse liver alcohol dehydrogenase derivatives.. Proc Natl Acad Sci U S A 1983 Sep;80(17):5289-93.
    doi: 10.1073/pnas.80.17.5289pmc: PMC384239pubmed: 6351056google scholar: lookup
  80. Sloan DL, Young JM, Mildvan AS. Nuclear magnetic resonance studies of substrate interaction with cobalt substituted alcohol dehydrogenase from liver.. Biochemistry 1975 May 6;14(9):1998-2008.
    doi: 10.1021/bi00680a030pubmed: 164901google scholar: lookup
  81. Dietrich H, Maret W, Wallén L, Zeppezauer M. Active-site-specific reconstituted cobalt(II) horse-liver alcohol dehydrogenase. Changes of the spectra of the substrate trans-4-(N,N-dimethylamino)-cinnamaldehyde and of the catalytic cobalt ion upon ternary complex formation with NADH and 1,4,5,6-tetrahydronicotinamide--adenine dinucleotide.. Eur J Biochem 1979 Oct;100(1):267-70.
    doi: 10.1111/j.1432-1033.1979.tb02057.xpubmed: 226360google scholar: lookup
  82. Sartorius C, Gerber M, Zeppezauer M, Dunn MF. Active-site cobalt(II)-substituted horse liver alcohol dehydrogenase: characterization of intermediates in the oxidation and reduction processes as a function of pH.. Biochemistry 1987 Feb 10;26(3):871-82.
    doi: 10.1021/bi00377a031pubmed: 3567150google scholar: lookup
  83. Drysdale BE, Hollis DP. A nuclear magnetic resonance study of cobalt II alcohol dehydrogenase: substrate analog-metal interactions.. Arch Biochem Biophys 1980 Nov;205(1):267-79.
    doi: 10.1016/0003-9861(80)90107-1pubmed: 7004359google scholar: lookup
  84. Andersson I, Maret W, Zeppezauer M, Brown RD 3rd, Koenig SH. Metal ion substitution at the catalytic site of horse-liver alcohol dehydrogenase: results from solvent magnetic relaxation studies. 1. Copper(II) and cobalt(II) ions.. Biochemistry 1981 Jun 9;20(12):3424-32.
    doi: 10.1021/bi00515a019pubmed: 7020751google scholar: lookup
  85. Zeppezauer M.. Coordination properties and mechanistic aspects of liver alcohol dehydrogenase. in The Coordination Chemistry of Metalloenzymes (Bertini I., Drago R. S., and Luchinat C., Eds.) pp 99–122, D. Reidel Publishing Co., Dordrecht, The Netherlands.
  86. Maret W, Makinen MW. The pH variation of steady-state kinetic parameters of site-specific Co(2+)-reconstituted liver alcohol dehydrogenase. A mechanistic probe for the assignment of metal-linked ionizations.. J Biol Chem 1991 Nov 5;266(31):20636-44.
    pubmed: 1939113
  87. Cook P. F., Cleland W. W.. Enzyme Kinetics and Mechanism. Taylor & Francis Group, LLC, New York.
  88. Brooks RL, Shore JD. The effects of pH and temperature on hydrogen transfer in the liver alcohol dehydrogenase mechanism.. J Biol Chem 1972 Apr 25;247(8):2382-3.
    pubmed: 4336373
  89. Kvassman J, Pettersson G. Effect of pH on the process of ternary-complex interconversion in the liver-alcohol-dehydrogenase reaction.. Eur J Biochem 1978 Jun 15;87(2):417-27.
    doi: 10.1111/j.1432-1033.1978.tb12391.xpubmed: 27359google scholar: lookup
  90. Sekhar VC, Plapp BV. Mechanism of binding of horse liver alcohol dehydrogenase and nicotinamide adenine dinucleotide.. Biochemistry 1988 Jul 12;27(14):5082-8.
    doi: 10.1021/bi00414a020pubmed: 3167032google scholar: lookup
  91. Shore JD, Santiago D. The role of metal in liver alcohol dehydrogenase catalysis. Spectral and kinetic studies with cobalt-substituted enzyme.. J Biol Chem 1975 Mar 25;250(6):2008-12.
    pubmed: 234953
  92. Bobsein BR, Myers RJ. 113Cd NMR in binary and ternary complexes of cadmium-substituted horse liver alcohol dehydrogenase.. J Biol Chem 1981 Jun 10;256(11):5313-6.
    pubmed: 7016851
  93. Schneider G, Cedergren-Zeppezauer E, Knight S, Eklund H, Zeppezauer M. Active site specific cadmium(II)-substituted horse liver alcohol dehydrogenase: crystal structures of the free enzyme, its binary complex with NADH, and the ternary complex with NADH and bound p-bromobenzyl alcohol.. Biochemistry 1985 Dec 3;24(25):7503-10.
    doi: 10.1021/bi00346a070pubmed: 2935190google scholar: lookup
  94. Andersson P, Kvassman J, Lindström A, Oldén B, Pettersson G. Evidence that ionization of zinc-bound water regulates the anion-binding capacity of the coenzyme-binding site in liver alcohol dehydrogenase.. Eur J Biochem 1980;108(1):303-12.
    doi: 10.1111/j.1432-1033.1980.tb04724.xpubmed: 6997039google scholar: lookup
  95. Eklund H, Samama JP, Wallén L. Pyrazole binding in crystalline binary and ternary complexes with liver alcohol dehydrogenase.. Biochemistry 1982 Sep 28;21(20):4858-66.
    doi: 10.1021/bi00263a005pubmed: 6753929google scholar: lookup
  96. Gilleland MJ, Shore JD. The limiting rate of chelation of liver alcohol dehydrogenase.. Biochem Biophys Res Commun 1970 Jul 13;40(1):230-5.
    doi: 10.1016/0006-291X(70)91071-5pubmed: 5456961google scholar: lookup
  97. Holyer R. H., Hubbard C. D., Kettle S. F. A., Wilkins R. G.. Kinetics of replacement reactions of complexes of transition metals with 1,10-phenanthroline and 2,2′-bipyridine. Inorg. Chem. 4, 929–935.
    doi: 10.1021/ic50029a002google scholar: lookup
  98. Henehan GT, Oppenheimer NJ. Horse liver alcohol dehydrogenase-catalyzed oxidation of aldehydes: dismutation precedes net production of reduced nicotinamide adenine dinucleotide.. Biochemistry 1993 Jan 26;32(3):735-8.
    doi: 10.1021/bi00054a001pubmed: 8422379google scholar: lookup
  99. Guy JE, Isupov MN, Littlechild JA. The structure of an alcohol dehydrogenase from the hyperthermophilic archaeon Aeropyrum pernix.. J Mol Biol 2003 Aug 29;331(5):1041-51.
    doi: 10.1016/S0022-2836(03)00857-Xpubmed: 12927540google scholar: lookup
  100. Pauly TA, Ekstrom JL, Beebe DA, Chrunyk B, Cunningham D, Griffor M, Kamath A, Lee SE, Madura R, Mcguire D, Subashi T, Wasilko D, Watts P, Mylari BL, Oates PJ, Adams PD, Rath VL. X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase.. Structure 2003 Sep;11(9):1071-85.
    doi: 10.1016/S0969-2126(03)00167-9pubmed: 12962626google scholar: lookup
  101. Kleifeld O, Shi SP, Zarivach R, Eisenstein M, Sagi I. The conserved Glu-60 residue in Thermoanaerobacter brockii alcohol dehydrogenase is not essential for catalysis.. Protein Sci 2003 Mar;12(3):468-79.
    doi: 10.1110/ps.0221603pmc: PMC2312447pubmed: 12592017google scholar: lookup
  102. Ryde U. The coordination of the catalytic zinc in alcohol dehydrogenase studied by combined quantum-chemical and molecular mechanics calculations.. J Comput Aided Mol Des 1996 Apr;10(2):153-64.
    doi: 10.1007/BF00402823pubmed: 8741019google scholar: lookup
  103. Ryde U. Molecular dynamics simulations of alcohol dehydrogenase with a four- or five-coordinate catalytic zinc ion.. Proteins 1995 Jan;21(1):40-56.
    doi: 10.1002/prot.340210106pubmed: 7716168google scholar: lookup
  104. Brünger AT. Free R value: a novel statistical quantity for assessing the accuracy of crystal structures.. Nature 1992 Jan 30;355(6359):472-5.
    doi: 10.1038/355472a0pubmed: 18481394google scholar: lookup

Citations

This article has been cited 17 times.
  1. Kasamatsu S, Nishimura A, Alam MM, Morita M, Shimoda K, Matsunaga T, Jung M, Ogata S, Barayeu U, Ida T, Nishida M, Nishimura A, Motohashi H, Akaike T. Supersulfide catalysis for nitric oxide and aldehyde metabolism. Sci Adv 2023 Aug 18;9(33):eadg8631.
    doi: 10.1126/sciadv.adg8631pubmed: 37595031google scholar: lookup
  2. Zheng C, Ji Z, Mathews II, Boxer SG. Enhanced active-site electric field accelerates enzyme catalysis. Nat Chem 2023 Aug 10;.
    doi: 10.1038/s41557-023-01287-xpubmed: 37563323google scholar: lookup
  3. Blacker TS, Duchen MR, Bain AJ. NAD(P)H binding configurations revealed by time-resolved fluorescence and two-photon absorption. Biophys J 2023 Apr 4;122(7):1240-1253.
    doi: 10.1016/j.bpj.2023.02.014pubmed: 36793214google scholar: lookup
  4. Bai X, Lan J, He S, Bu T, Zhang J, Wang L, Jin X, Mao Y, Guan W, Zhang L, Lu M, Piao H, Jo I, Quan C, Nam KH, Xu Y. Structural and Biochemical Analyses of the Butanol Dehydrogenase from Fusobacterium nucleatum. Int J Mol Sci 2023 Feb 3;24(3).
    doi: 10.3390/ijms24032994pubmed: 36769315google scholar: lookup
  5. Langley C, Tatsis E, Hong B, Nakamura Y, Paetz C, Stevenson CEM, Basquin J, Lawson DM, Caputi L, O'Connor SE. Expansion of the Catalytic Repertoire of Alcohol Dehydrogenases in Plant Metabolism. Angew Chem Int Ed Engl 2022 Nov 25;61(48):e202210934.
    doi: 10.1002/anie.202210934pubmed: 36198083google scholar: lookup
  6. Plapp BV, Gakhar L, Subramanian R. Dependence of crystallographic atomic displacement parameters on temperature (25-150 K) for complexes of horse liver alcohol dehydrogenase. Acta Crystallogr D Struct Biol 2022 Oct 1;78(Pt 10):1221-1234.
    doi: 10.1107/S2059798322008361pubmed: 36189742google scholar: lookup
  7. Rapp C, Nidetzky B. Hydride Transfer Mechanism of Enzymatic Sugar Nucleotide C2 Epimerization Probed with a Loose-Fit CDP-Glucose Substrate. ACS Catal 2022 Jun 17;12(12):6816-6830.
    doi: 10.1021/acscatal.2c00257pubmed: 35747200google scholar: lookup
  8. Pal S, Plapp BV. The Thr45Gly substitution in yeast alcohol dehydrogenase substantially decreases catalysis, alters pH dependencies, and disrupts the proton relay system. Chem Biol Interact 2021 Nov 1;349:109650.
    doi: 10.1016/j.cbi.2021.109650pubmed: 34529977google scholar: lookup
  9. Plapp BV, Subramanian R. Alternative binding modes in abortive NADH-alcohol complexes of horse liver alcohol dehydrogenase. Arch Biochem Biophys 2021 Apr 15;701:108825.
    doi: 10.1016/j.abb.2021.108825pubmed: 33675814google scholar: lookup
  10. Blacker TS, Mistry N, Plotegher N, Westbrook ER, Sewell MDE, Carroll J, Szabadkai G, Bain AJ, Duchen MR. Redox-dependent binding and conformational equilibria govern the fluorescence decay of NAD(P)H in living cells. FEBS Lett 2025 Oct;599(19):2802-2816.
    doi: 10.1002/1873-3468.70125pubmed: 40878865google scholar: lookup
  11. Carr SC, O'Connor SE. A Tight-Knit Family: The Medium-Chain Dehydrogenase/Reductases of Monoterpene Indole Alkaloid Biosynthesis. Biochemistry 2025 Jul 1;64(13):2712-2726.
    doi: 10.1021/acs.biochem.5c00234pubmed: 40536199google scholar: lookup
  12. Nigl A, Delsoglio V, Sovic L, Grgić M, Malihan-Yap L, Myrtollari K, Spasic J, Winkler M, Oberdorfer G, Taden A, Anić I, Kourist R. Engineering of Transmembrane Alkane Monooxygenases to Improve a Key Reaction Step in the Synthesis of Polymer Precursor Tulipalin A. Angew Chem Int Ed Engl 2025 Jun 17;64(25):e202503464.
    doi: 10.1002/anie.202503464pubmed: 40116655google scholar: lookup
  13. Camargo PG, da Silva RB, Zuma AA, Garden SJ, Albuquerque MG, Rodrigues CR, da Silva Lima CH. In silico evaluation of N-aryl-1,10-phenanthroline-2-amines as potential inhibitors of T. cruzi GP63 zinc-metalloprotease by docking and molecular dynamics simulations. Sci Rep 2025 Feb 19;15(1):6036.
    doi: 10.1038/s41598-025-90088-ypubmed: 39971997google scholar: lookup
  14. Gemmecker Y, Winiarska A, Hege D, Kahnt J, Seubert A, Szaleniec M, Heider J. A pH-dependent shift of redox cofactor specificity in a benzyl alcohol dehydrogenase of aromatoleum aromaticum EbN1. Appl Microbiol Biotechnol 2024 Jul 8;108(1):410.
    doi: 10.1007/s00253-024-13225-zpubmed: 38976076google scholar: lookup
  15. Hagedoorn PL, Pabst M, Hanefeld U. The metal cofactor: stationary or mobile?. Appl Microbiol Biotechnol 2024 Jun 24;108(1):391.
    doi: 10.1007/s00253-024-13206-2pubmed: 38910188google scholar: lookup
  16. Jacobi T, Kratzer DA, Plapp BV. Substitution of both histidines in the active site of yeast alcohol dehydrogenase 1 exposes underlying pH dependencies. Chem Biol Interact 2024 May 1;394:110992.
    doi: 10.1016/j.cbi.2024.110992pubmed: 38579923google scholar: lookup
  17. Plapp BV, Kratzer DA, Souhrada SK, Warth E, Jacobi T. Specific base catalysis by yeast alcohol dehydrogenase I with substitutions of histidine-48 by glutamate or serine residues in the proton relay system. Chem Biol Interact 2023 Sep 1;382:110558.
    doi: 10.1016/j.cbi.2023.110558pubmed: 37247811google scholar: lookup
Subscribe to our newsletter
Join 99,493 horse owners like you who receive our email updates on horse health and nutrition.