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1zk1
From Proteopedia
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|PDB= 1zk1 |SIZE=350|CAPTION= <scene name='initialview01'>1zk1</scene>, resolution 1.78Å | |PDB= 1zk1 |SIZE=350|CAPTION= <scene name='initialview01'>1zk1</scene>, resolution 1.78Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=AC0:1-PHENYLETHANONE'>AC0</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Alcohol_dehydrogenase_(NADP(+)) Alcohol dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.2 1.1.1.2] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Alcohol_dehydrogenase_(NADP(+)) Alcohol dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.2 1.1.1.2] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1nxq|1NXQ]], [[1zjy|1ZJY]], [[1zjz|1ZJZ]], [[1zk0|1ZK0]], [[1zk2|1ZK2]], [[1zk3|1ZK3]], [[1zk4|1ZK4]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zk1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zk1 OCA], [http://www.ebi.ac.uk/pdbsum/1zk1 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zk1 RCSB]</span> | ||
}} | }} | ||
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[[Category: Schlieben, N H.]] | [[Category: Schlieben, N H.]] | ||
[[Category: Schomburg, D.]] | [[Category: Schomburg, D.]] | ||
| - | [[Category: AC0]] | ||
| - | [[Category: MG]] | ||
| - | [[Category: NAD]] | ||
[[Category: magnesium dependence]] | [[Category: magnesium dependence]] | ||
[[Category: r-specific alcohol dehydrogenase]] | [[Category: r-specific alcohol dehydrogenase]] | ||
[[Category: short chain reductases/dehydrogenase]] | [[Category: short chain reductases/dehydrogenase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:37:44 2008'' |
Revision as of 22:37, 30 March 2008
| |||||||
| , resolution 1.78Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | Alcohol dehydrogenase (NADP(+)), with EC number 1.1.1.2 | ||||||
| Related: | 1NXQ, 1ZJY, 1ZJZ, 1ZK0, 1ZK2, 1ZK3, 1ZK4
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structure of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis in complex with phenylethanol and NAD
Overview
The R-specific alcohol dehydrogenase (RADH) from Lactobacillus brevis is an NADP-dependent, homotetrameric member of the extended enzyme family of short-chain dehydrogenases/reductases (SDR) with a high biotechnological application potential. Its preferred in vitro substrates are prochiral ketones like acetophenone with almost invariably a small methyl group as one substituent and a bulky (often aromatic) moiety as the other. On the basis of an atomic-resolution structure of wild-type RADH in complex with NADP and acetophenone, we designed the mutant RADH-G37D, which should possess an improved cosubstrate specificity profile for biotechnological purposes, namely, a preference for NAD rather than NADP. Comparative kinetic measurements with wild-type and mutant RADH showed that this aim was achieved. To characterize the successful mutant structurally, we determined several, partly atomic-resolution, crystal structures of RADH-G37D both as an apo-enzyme and as ternary complex with NAD or NADH and phenylethanol. The increased affinity of RADH-G37D for NAD(H) depends on an interaction between the adenosine ribose moiety of NAD and the inserted aspartate side-chain. A structural comparison between RADH-G37D as apo-enzyme and as a part of a ternary complex revealed significant rearrangements of Ser141, Glu144, Tyr189 and Met205 in the vicinity of the active site. This plasticity contributes to generate a small hydrophobic pocket for the methyl group typical for RADH substrates, and a hydrophobic coat for the second, more variable and often aromatic, substituent. Around Ser141 we even found alternative conformations in the backbone. A structural adaptability in this region, which we describe here for the first time for an SDR enzyme, is probably functionally important, because it concerns Ser142, a member of the highly conserved catalytic tetrad typical for SDR enzymes. Moreover, it affects an extended proton relay system that has been identified recently as a critical element for the catalytic mechanism in SDR enzymes.
About this Structure
1ZK1 is a Single protein structure of sequence from Lactobacillus brevis. Full crystallographic information is available from OCA.
Reference
Atomic resolution structures of R-specific alcohol dehydrogenase from Lactobacillus brevis provide the structural bases of its substrate and cosubstrate specificity., Schlieben NH, Niefind K, Muller J, Riebel B, Hummel W, Schomburg D, J Mol Biol. 2005 Jun 17;349(4):801-13. PMID:15896805
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