1b2l

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[[Image:1b2l.jpg|left|200px]]
[[Image:1b2l.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 1b2l |SIZE=350|CAPTION= <scene name='initialview01'>1b2l</scene>, resolution 1.6&Aring;
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The line below this paragraph, containing "STRUCTURE_1b2l", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=ACA:Catalytic+Triad'>ACA</scene>, <scene name='pdbsite=CAA:Ca2++Binding+Residues'>CAA</scene>, <scene name='pdbsite=NA1:Nad+Binding+Motif+In+Dadhs+G(A)Xgxxg'>NA1</scene>, <scene name='pdbsite=NA2:Nad+Binding+Motif+In+Sdrs+Gxxxgxg'>NA2</scene> and <scene name='pdbsite=NA3:Nad/Nadp+Selectivity+Amino+Acid'>NA3</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CYH:CYCLOHEXANONE'>CYH</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=NDC:NICOTINAMIDE+ADENINE+DINUCLEOTIDE+CYCLOHEXANONE'>NDC</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Alcohol_dehydrogenase Alcohol dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.1 1.1.1.1] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_1b2l| PDB=1b2l | SCENE= }}
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|RELATEDENTRY=[[1b15|1B15]], [[1b14|1B14]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1b2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b2l OCA], [http://www.ebi.ac.uk/pdbsum/1b2l PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1b2l RCSB]</span>
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}}
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'''ALCOHOL DEHYDROGENASE FROM DROSOPHILA LEBANONENSIS: TERNARY COMPLEX WITH NAD-CYCLOHEXANONE'''
'''ALCOHOL DEHYDROGENASE FROM DROSOPHILA LEBANONENSIS: TERNARY COMPLEX WITH NAD-CYCLOHEXANONE'''
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[[Category: Gonzalez-Duarte, R.]]
[[Category: Gonzalez-Duarte, R.]]
[[Category: Ladenstein, R.]]
[[Category: Ladenstein, R.]]
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[[Category: alcohol dehydrogenase]]
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[[Category: Alcohol dehydrogenase]]
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[[Category: detoxification]]
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[[Category: Detoxification]]
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[[Category: drosophila lebanonensis]]
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[[Category: Drosophila lebanonensis]]
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[[Category: metabolism]]
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[[Category: Metabolism]]
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[[Category: nad- cyclohexanone adduct]]
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[[Category: Nad- cyclohexanone adduct]]
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[[Category: oxidoreductase]]
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[[Category: Oxidoreductase]]
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[[Category: short-chain dehydrogenases/reductase]]
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[[Category: Short-chain dehydrogenases/reductase]]
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[[Category: ternary complex]]
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[[Category: Ternary complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:58:51 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:52:23 2008''
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Revision as of 07:58, 2 May 2008

Image:1b2l.jpg

Template:STRUCTURE 1b2l

ALCOHOL DEHYDROGENASE FROM DROSOPHILA LEBANONENSIS: TERNARY COMPLEX WITH NAD-CYCLOHEXANONE


Overview

Drosophila alcohol dehydrogenase (DADH) is an NAD+-dependent enzyme that catalyzes the oxidation of alcohols to aldehydes/ketones. DADH is the member of the short-chain dehydrogenases/reductases family (SDR) for which the largest amount of biochemical data has been gathered during the last three decades. The crystal structures of one binary form (NAD+) and three ternary complexes with NAD+.acetone, NAD+.3-pentanone and NAD+.cyclohexanone were solved at 2.4, 2.2, 1. 4 and 1.6 A resolution, respectively. From the molecular interactions observed, the reaction mechanism could be inferred. The structure of DADH undergoes a conformational change in order to bind the coenzyme. Furthermore, upon binding of the ketone, a region that was disordered in the apo form (186-191) gets stabilized and closes the active site cavity by creating either a small helix (NAD+. acetone, NAD+.3-pentanone) or an ordered loop (NAD+.cyclohexanone). The active site pocket comprises a hydrophobic bifurcated cavity which explains why the enzyme is more efficient in oxidizing secondary aliphatic alcohols (preferably R form) than primary ones. Difference Fourier maps showed that the ketone inhibitor molecule has undergone a covalent reaction with the coenzyme in all three ternary complexes. Due to the presence of the positively charged ring of the coenzyme (NAD+) and the residue Lys155, the amino acid Tyr151 is in its deprotonated (tyrosinate) state at physiological pH. Tyr151 can subtract a proton from the enolic form of the ketone and catalyze a nucleophilic attack of the Calphaatom to the C4 position of the coenzyme creating an NAD-ketone adduct. The binding of these NAD-ketone adducts to DADH accounts for the inactivation of the enzyme. The catalytic reaction proceeds in a similar way, involving the same amino acids as in the formation of the NAD-ketone adduct. The p Kavalue of 9-9.5 obtained by kinetic measurements on apo DADH can be assigned to a protonated Tyr151 which is converted to an unprotonated tyrosinate (p Ka7.6) by the influence of the positively charged nicotinamide ring in the binary enzyme-NAD+form. pH independence during the release of NADH from the binary complex enzyme-NADH can be explained by either a lack of electrostatic interaction between the coenzyme and Tyr151 or an apparent p Kavalue for this residue higher than 10.0.

About this Structure

1B2L is a Single protein structure of sequence from Scaptodrosophila lebanonensis. Full crystallographic information is available from OCA.

Reference

The catalytic reaction and inhibition mechanism of Drosophila alcohol dehydrogenase: observation of an enzyme-bound NAD-ketone adduct at 1.4 A resolution by X-ray crystallography., Benach J, Atrian S, Gonzalez-Duarte R, Ladenstein R, J Mol Biol. 1999 Jun 4;289(2):335-55. PMID:10366509 Page seeded by OCA on Fri May 2 10:58:51 2008

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