1b15: Difference between revisions
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[[Image:1b15.gif|left|200px]] | [[Image:1b15.gif|left|200px]] | ||
'''ALCOHOL DEHYDROGENASE FROM DROSOPHILA LEBANONENSIS TERNARY COMPLEX WITH NAD-ACETONE''' | {{Structure | ||
|PDB= 1b15 |SIZE=350|CAPTION= <scene name='initialview01'>1b15</scene>, resolution 2.2Å | |||
|SITE= <scene name='pdbsite=ACA:Catalytic+Triad'>ACA</scene>, <scene name='pdbsite=ACB:Catalytic+Triad'>ACB</scene>, <scene name='pdbsite=CAA:Ca2++Binding+Residues'>CAA</scene>, <scene name='pdbsite=CAB:Ca2++Binding+Residues'>CAB</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>, <scene name='pdbsite=NA3:Nad/Nadp+Selectivity+Amino+Acid'>NA3</scene>, <scene name='pdbsite=NB1:Nad+Binding+Motif+In+Dadhs+G(A)Xgxxg'>NB1</scene>, <scene name='pdbsite=NB2:Nad+Binding+Motif+In+Sdrs+Gxxxgxg'>NB2</scene> and <scene name='pdbsite=NB3:Nad/Nadp+Selectivity+Amino+Acid'>NB3</scene> | |||
|LIGAND= <scene name='pdbligand=NAE:NICOTINAMIDE ADENINE DINUCLEOTIDE ACETONE ADDUCT'>NAE</scene> | |||
|ACTIVITY= [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] | |||
|GENE= | |||
}} | |||
'''ALCOHOL DEHYDROGENASE FROM DROSOPHILA LEBANONENSIS TERNARY COMPLEX WITH NAD-ACETONE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1B15 is a [ | 1B15 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Scaptodrosophila_lebanonensis Scaptodrosophila lebanonensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B15 OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/10366509 10366509] | ||
[[Category: Alcohol dehydrogenase]] | [[Category: Alcohol dehydrogenase]] | ||
[[Category: Scaptodrosophila lebanonensis]] | [[Category: Scaptodrosophila lebanonensis]] | ||
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[[Category: nad- acetone adduct]] | [[Category: nad- acetone adduct]] | ||
[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
[[Category: short-chain dehydrogenases/ | [[Category: short-chain dehydrogenases/reductase]] | ||
[[Category: ternary complex]] | [[Category: ternary complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:04:59 2008'' | ||
Revision as of 11:04, 20 March 2008
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| , resolution 2.2Å | |||||||
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| Sites: | , , , , , , , , and | ||||||
| Ligands: | |||||||
| Activity: | Alcohol dehydrogenase, with EC number 1.1.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
ALCOHOL DEHYDROGENASE FROM DROSOPHILA LEBANONENSIS TERNARY COMPLEX WITH NAD-ACETONE
OverviewOverview
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 StructureAbout this Structure
1B15 is a Single protein structure of sequence from Scaptodrosophila lebanonensis. Full crystallographic information is available from OCA.
ReferenceReference
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
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