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| ==Orthorhombic crystal structure of the apo-form of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis== | | ==Orthorhombic crystal structure of the apo-form of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis== |
| <StructureSection load='1zk2' size='340' side='right' caption='[[1zk2]], [[Resolution|resolution]] 1.55Å' scene=''> | | <StructureSection load='1zk2' size='340' side='right'caption='[[1zk2]], [[Resolution|resolution]] 1.55Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[1zk2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_casei_g"_von_freudenreich_and_thoni_1904 "bacillus casei g" von freudenreich and thoni 1904]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZK2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ZK2 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1zk2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Levilactobacillus_brevis Levilactobacillus brevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZK2 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.55Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nxq|1nxq]], [[1zjy|1zjy]], [[1zjz|1zjz]], [[1zk0|1zk0]], [[1zk1|1zk1]], [[1zk3|1zk3]], [[1zk4|1zk4]]</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zk2 OCA], [https://pdbe.org/1zk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zk2 RCSB], [https://www.ebi.ac.uk/pdbsum/1zk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zk2 ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zk2 OCA], [http://pdbe.org/1zk2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1zk2 RCSB], [http://www.ebi.ac.uk/pdbsum/1zk2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1zk2 ProSAT]</span></td></tr> | |
| </table> | | </table> |
| | == Function == |
| | [https://www.uniprot.org/uniprot/Q84EX5_LEVBR Q84EX5_LEVBR] |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1zk2 ConSurf]. | | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1zk2 ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| 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.
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| 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<ref>PMID:15896805</ref>
| | ==See Also== |
| | | *[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 1zk2" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Bacillus casei g von freudenreich and thoni 1904]] | | [[Category: Large Structures]] |
| [[Category: Hummel, W]] | | [[Category: Levilactobacillus brevis]] |
| [[Category: Muller, J]] | | [[Category: Hummel W]] |
| [[Category: Niefind, K]] | | [[Category: Muller J]] |
| [[Category: Riebel, B]] | | [[Category: Niefind K]] |
| [[Category: Schlieben, N H]] | | [[Category: Riebel B]] |
| [[Category: Schomburg, D]] | | [[Category: Schlieben NH]] |
| [[Category: Magnesium dependence]]
| | [[Category: Schomburg D]] |
| [[Category: Oxidoreductase]]
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| [[Category: R-specific alcohol dehydrogenase]]
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| [[Category: Short chain reductases/dehydrogenase]]
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