1zk2: Difference between revisions
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[[Image:1zk2.gif|left|200px]] | [[Image:1zk2.gif|left|200px]] | ||
'''Orthorhombic crystal structure of the apo-form of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis''' | {{Structure | ||
|PDB= 1zk2 |SIZE=350|CAPTION= <scene name='initialview01'>1zk2</scene>, resolution 1.55Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM ION'>MG</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] | |||
|GENE= | |||
}} | |||
'''Orthorhombic crystal structure of the apo-form of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1ZK2 is a [ | 1ZK2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_brevis Lactobacillus brevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZK2 OCA]. | ||
==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:// | 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: Alcohol dehydrogenase (NADP(+))]] | ||
[[Category: Lactobacillus brevis]] | [[Category: Lactobacillus brevis]] | ||
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[[Category: magnesium dependence]] | [[Category: magnesium dependence]] | ||
[[Category: r-specific alcohol dehydrogenase]] | [[Category: r-specific alcohol dehydrogenase]] | ||
[[Category: short chain reductases/ | [[Category: short chain reductases/dehydrogenase]] | ||
''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 15:36:27 2008'' | ||
Revision as of 13:36, 20 March 2008
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| 1zk2, resolution 1.55Å | |||||||||||||
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| Ligands: | MG | ||||||||||||
| Activity: | Alcohol dehydrogenase (NADP(+)), with EC number 1.1.1.2 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Orthorhombic 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
1ZK2 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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