Einzeltreffer — DigiBib

Enzymes typically have high specificity for their substrates, but the structures of substrates and products differ, and multiple modes of binding are observed. In this study, high resolution X-ray crystallography of complexes with NADH and alcohols show alternative modes of binding in the active site. Enzyme crystallized with the good substrates NAD + and 4-methylbenzyl alcohol was found to be an abortive complex of NADH with 4-methylbenzyl alcohol rotated to a "non-productive" mode as compared to the structures that resemble reactive Michaelis complexes with NAD + and 2,2,2-trifluoroethanol or 2,3,4,5,6-pentafluorobenzyl alcohol. The NADH is formed by reduction of the NAD + with the alcohol during the crystallization. The same structure was also formed by directly crystallizing the enzyme with NADH and 4-methylbenzyl alcohol. Crystals prepared with NAD + and 4-bromobenzyl alcohol also form the abortive complex with NADH. Surprisingly, crystals prepared with NAD + and the strong inhibitor 1H,1H-heptafluorobutanol also had NADH, and the alcohol was bound in two different conformations that illustrate binding flexibility. Oxidation of 2-methyl-2,4-pentanediol during the crystallization apparently led to reduction of the NAD + . Kinetic studies show that high concentrations of alcohols can bind to the enzyme-NADH complex and activate or inhibit the enzyme. Together with previous studies on complexes with NADH and formamide analogues of the carbonyl substrates, models for the Michaelis complexes with NAD + -alcohol and NADH-aldehyde are proposed.

Titel:	Alternative binding modes in abortive NADH-alcohol complexes of horse liver alcohol dehydrogenase.
Autor/in / Beteiligte Person:	Plapp, BV ; Subramanian, R
Link:	Zum Volltext
Zeitschrift:	Archives of biochemistry and biophysics, Jg. 701 (2021-04-15), S. 108825
Veröffentlichung:	<2000- > : San Diego, CA : Elsevier ; <i>Original Publication</i>: New York, NY : Academic Press, 2021
Medientyp:	academicJournal
ISSN:	1096-0384 (electronic)
DOI:	10.1016/j.abb.2021.108825
Schlagwort:	Animals Binding Sites Catalytic Domain Crystallography, X-Ray Alcohol Dehydrogenase chemistry Alcohols chemistry Horses Liver enzymology Models, Chemical NAD chemistry
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural Language: English [Arch Biochem Biophys] 2021 Apr 15; Vol. 701, pp. 108825. <i>Date of Electronic Publication: </i>2021 Mar 03. MeSH Terms: Horses* ; Models, Chemical* ; Alcohol Dehydrogenase / chemistry ; Alcohols / chemistry ; Liver / enzymology ; NAD / chemistry ; Animals ; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray References: Biochemistry. 2012 May 15;51(19):4035-48. (PMID: 22531044) ; Biochemistry. 1997 Mar 25;36(12):3522-7. (PMID: 9132002) ; Biochemistry. 2020 Feb 25;59(7):862-879. (PMID: 31994873) ; Biochemistry. 1994 May 3;33(17):5230-7. (PMID: 8172897) ; Biochemistry. 2007 May 8;46(18):5446-54. (PMID: 17429946) ; J Am Chem Soc. 2001 Nov 14;123(45):11262-72. (PMID: 11697969) ; J Chem Phys. 2004 Mar 1;120(9):4247-50. (PMID: 15268592) ; Acta Crystallogr D Biol Crystallogr. 2001 Aug;57(Pt 8):1201-3. (PMID: 11468417) ; J Biol Chem. 1991 Jul 15;266(20):13296-302. (PMID: 1712777) ; Protein Sci. 2018 Jan;27(1):293-315. (PMID: 29067766) ; J Biol Chem. 2001 Mar 23;276(12):9316-21. (PMID: 11134046) ; Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42. (PMID: 21460441) ; Proc Natl Acad Sci U S A. 2010 May 25;107(21):9572-7. (PMID: 20457944) ; J Mol Biol. 1978 Jun 15;122(1):23-32. (PMID: 209195) ; J Biol Chem. 1980 Feb 25;255(4):1509-14. (PMID: 6986372) ; Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):355-67. (PMID: 21460454) ; J Biol Chem. 2003 Sep 19;278(38):36699-706. (PMID: 12855684) ; Biochemistry. 1997 Jan 14;36(2):382-9. (PMID: 9003191) ; Biochemistry. 2017 Jul 18;56(28):3632-3646. (PMID: 28640600) ; J Biol Chem. 1982 Dec 10;257(23):14349-58. (PMID: 6754727) ; Protein Sci. 2018 Mar;27(3):750-768. (PMID: 29271062) ; Eur J Biochem. 1981 Mar;114(3):555-63. (PMID: 7016531) ; Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9. (PMID: 2025413) ; Biochemistry. 1974 Sep 24;13(20):4185-91. (PMID: 4370301) ; Biochemistry. 2005 Sep 27;44(38):12797-808. (PMID: 16171395) ; Biochemistry. 2004 Mar 23;43(11):3014-26. (PMID: 15023053) ; Nature. 1992 Jan 30;355(6359):472-5. (PMID: 18481394) ; Biochemistry. 2003 Mar 18;42(10):2907-15. (PMID: 12627956) ; J Am Chem Soc. 2001 Dec 5;123(48):11952-9. (PMID: 11724603) ; Biochemistry. 1998 Oct 6;37(40):14267-78. (PMID: 9760265) ; FEBS Lett. 1979 Apr 1;100(1):17-22. (PMID: 220086) ; Acta Crystallogr C Struct Chem. 2015 Jan;71(Pt 1):3-8. (PMID: 25567568) ; Chem Biol Interact. 2017 Oct 1;276:77-87. (PMID: 28025168) ; Acta Crystallogr D Biol Crystallogr. 1999 Oct;55(Pt 10):1718-25. (PMID: 10531521) ; Biochemistry. 1993 Oct 19;32(41):11186-94. (PMID: 8218182) ; Biochemistry. 1990 May 8;29(18):4289-95. (PMID: 2161681) ; Eur J Biochem. 1974 Dec 16;50(1):113-8. (PMID: 4375561) ; Eur J Biochem. 1980 Feb;103(3):565-75. (PMID: 6987061) ; Eur J Biochem. 1981 Jan;113(3):425-33. (PMID: 7011796) ; Acta Crystallogr D Biol Crystallogr. 1999 Dec;55(Pt 12):1997-2004. (PMID: 10666575) ; Biochemistry. 2014 Feb 11;53(5):881-94. (PMID: 24437493) ; Biochemistry. 2002 Dec 31;41(52):15770-9. (PMID: 12501206) ; Biochemistry. 1977 Jun 14;16(12):2716-25. (PMID: 19037) ; Acta Crystallogr D Biol Crystallogr. 1994 Nov 1;50(Pt 6):793-807. (PMID: 15299346) Grant Information: R01 AA000279 United States AA NIAAA NIH HHS; R01 GM078446 United States GM NIGMS NIH HHS Contributed Indexing: Keywords: 1H,1H-heptafluorobutanol; 4-Bromobenzyl alcohol; 4-Methylbenzyl alcohol; Hydrogen transfer; X-ray crystallography Substance Nomenclature: 0 (Alcohols) ; 0U46U6E8UK (NAD) ; EC 1.1.1.1 (Alcohol Dehydrogenase) Entry Date(s): Date Created: 20210306 Date Completed: 20210420 Latest Revision: 20240331 Update Code: 20240331 PubMed Central ID: PMC7980771

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Alternative binding modes in abortive NADH-alcohol complexes of horse liver alcohol dehydrogenase.