1zk3
From Proteopedia
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'''Triclinic crystal structure of the apo-form of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis''' | '''Triclinic crystal structure of the apo-form of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis''' | ||
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==Reference== | ==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:[http://www.ncbi.nlm.nih.gov/pubmed/15896805 15896805] | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15896805 15896805] | ||
| - | [[Category: Alcohol dehydrogenase (NADP(+))]] | ||
[[Category: Lactobacillus brevis]] | [[Category: Lactobacillus brevis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Schlieben, N H.]] | [[Category: Schlieben, N H.]] | ||
[[Category: Schomburg, D.]] | [[Category: Schomburg, D.]] | ||
| - | [[Category: | + | [[Category: Magnesium dependence]] |
| - | [[Category: | + | [[Category: R-specific alcohol dehydrogenase]] |
| - | [[Category: | + | [[Category: Short chain reductases/dehydrogenase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:43:15 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 14:43, 3 May 2008
Triclinic crystal structure of the apo-form of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis
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
1ZK3 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 Page seeded by OCA on Sat May 3 17:43:15 2008
