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| - | [[Image:1zk3.gif|left|200px]] | |
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| - | {{Structure
| + | ==Triclinic crystal structure of the apo-form of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis== |
| - | |PDB= 1zk3 |SIZE=350|CAPTION= <scene name='initialview01'>1zk3</scene>, resolution 2.2Å
| + | <StructureSection load='1zk3' size='340' side='right'caption='[[1zk3]], [[Resolution|resolution]] 2.20Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>
| + | <table><tr><td colspan='2'>[[1zk3]] is a 8 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=1ZK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZK3 FirstGlance]. <br> |
| - | |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>
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | |GENE=
| + | <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> |
| - | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zk3 OCA], [https://pdbe.org/1zk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zk3 RCSB], [https://www.ebi.ac.uk/pdbsum/1zk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zk3 ProSAT]</span></td></tr> |
| - | |RELATEDENTRY=[[1nxq|1NXQ]], [[1zjy|1ZJY]], [[1zjz|1ZJZ]], [[1zk0|1ZK0]], [[1zk1|1ZK1]], [[1zk2|1ZK2]], [[1zk4|1ZK4]]
| + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zk3 OCA], [http://www.ebi.ac.uk/pdbsum/1zk3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zk3 RCSB]</span>
| + | == Function == |
| - | }}
| + | [https://www.uniprot.org/uniprot/Q84EX5_LEVBR Q84EX5_LEVBR] |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zk/1zk3_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </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=1zk3 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''Triclinic crystal structure of the apo-form of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis'''
| + | ==See Also== |
| - | | + | *[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]] |
| - | | + | __TOC__ |
| - | ==Overview== | + | </StructureSection> |
| - | 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.
| + | [[Category: Large Structures]] |
| - | | + | [[Category: Levilactobacillus brevis]] |
| - | ==About this Structure==
| + | [[Category: Hummel W]] |
| - | 1ZK3 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=1ZK3 OCA].
| + | [[Category: Muller J]] |
| - | | + | [[Category: Niefind K]] |
| - | ==Reference==
| + | [[Category: Riebel B]] |
| - | 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: Schlieben NH]] |
| - | [[Category: Alcohol dehydrogenase (NADP(+))]] | + | [[Category: Schomburg D]] |
| - | [[Category: Lactobacillus brevis]] | + | |
| - | [[Category: Single protein]]
| + | |
| - | [[Category: Hummel, W.]] | + | |
| - | [[Category: Muller, J.]] | + | |
| - | [[Category: Niefind, K.]] | + | |
| - | [[Category: Riebel, B.]] | + | |
| - | [[Category: Schlieben, N H.]] | + | |
| - | [[Category: Schomburg, D.]] | + | |
| - | [[Category: magnesium dependence]]
| + | |
| - | [[Category: r-specific alcohol dehydrogenase]]
| + | |
| - | [[Category: short chain reductases/dehydrogenase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:37:44 2008''
| + | |
