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[[Image:1zk1.gif|left|200px]]<br /><applet load="1zk1" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1zk1, resolution 1.78&Aring;" />
'''Structure of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis in complex with phenylethanol and NAD'''<br />


==Overview==
==Structure of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis in complex with phenylethanol and NAD==
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.
<StructureSection load='1zk1' size='340' side='right'caption='[[1zk1]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1zk1]] 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=1ZK1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZK1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.78&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></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=1zk1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zk1 OCA], [https://pdbe.org/1zk1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zk1 RCSB], [https://www.ebi.ac.uk/pdbsum/1zk1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zk1 ProSAT]</span></td></tr>
</table>
== 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/1zk1_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=1zk1 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1ZK1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Lactobacillus_brevis Lactobacillus brevis] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=NAD:'>NAD</scene> and <scene name='pdbligand=AC0:'>AC0</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZK1 OCA].
*[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
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://ispc.weizmann.ac.il//pmbin/getpm?pmid=15896805 15896805]
[[Category: Large Structures]]
[[Category: Alcohol dehydrogenase (NADP(+))]]
[[Category: Levilactobacillus brevis]]
[[Category: Lactobacillus brevis]]
[[Category: Hummel W]]
[[Category: Single protein]]
[[Category: Muller J]]
[[Category: Hummel, W.]]
[[Category: Niefind K]]
[[Category: Muller, J.]]
[[Category: Riebel B]]
[[Category: Niefind, K.]]
[[Category: Schlieben NH]]
[[Category: Riebel, B.]]
[[Category: Schomburg D]]
[[Category: Schlieben, N H.]]
[[Category: Schomburg, D.]]
[[Category: AC0]]
[[Category: MG]]
[[Category: NAD]]
[[Category: magnesium dependence]]
[[Category: r-specific alcohol dehydrogenase]]
[[Category: short chain reductases/dehydrogenases]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:16:25 2008''

Latest revision as of 12:05, 14 February 2024

Structure of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis in complex with phenylethanol and NADStructure of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis in complex with phenylethanol and NAD

Structural highlights

1zk1 is a 1 chain structure with sequence from Levilactobacillus brevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.78Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q84EX5_LEVBR

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1zk1, resolution 1.78Å

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