2vss: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 3: | Line 3: | ||
<StructureSection load='2vss' size='340' side='right'caption='[[2vss]], [[Resolution|resolution]] 2.22Å' scene=''> | <StructureSection load='2vss' size='340' side='right'caption='[[2vss]], [[Resolution|resolution]] 2.22Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2vss]] is a 6 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2vss]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_fluorescens Pseudomonas fluorescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VSS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VSS FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.22Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=V55:4-HYDROXY-3-METHOXYBENZALDEHYDE'>V55</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=2vss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vss OCA], [https://pdbe.org/2vss PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vss RCSB], [https://www.ebi.ac.uk/pdbsum/2vss PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vss ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/HCHL_PSEFL HCHL_PSEFL] Catalyzes the hydration of the acyl-CoA thioester of ferulic acid and the subsequent retro-aldol cleavage of the hydrated intermediate to yield vanillin (4-hydroxy-3-methoxy-benzaldehyde).<ref>PMID:9461612</ref> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 34: | Line 33: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Pseudomonas fluorescens]] | ||
[[Category: Bennett | [[Category: Bennett JP]] | ||
[[Category: Bertin | [[Category: Bertin LM]] | ||
[[Category: Brzozowski | [[Category: Brzozowski AM]] | ||
[[Category: Grogan | [[Category: Grogan G]] | ||
[[Category: Walton | [[Category: Walton NJ]] | ||
Latest revision as of 18:30, 13 December 2023
Wild-type Hydroxycinnamoyl-CoA hydratase lyase in complex with acetyl- CoA and vanillinWild-type Hydroxycinnamoyl-CoA hydratase lyase in complex with acetyl- CoA and vanillin
Structural highlights
FunctionHCHL_PSEFL Catalyzes the hydration of the acyl-CoA thioester of ferulic acid and the subsequent retro-aldol cleavage of the hydrated intermediate to yield vanillin (4-hydroxy-3-methoxy-benzaldehyde).[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHCHL (hydroxycinnamoyl-CoA hydratase-lyase) catalyses the biotransformation of feruloyl-CoA to acetyl-CoA and the important flavour-fragrance compound vanillin (4-hydroxy-3-methoxybenzaldehyde) and is exploited in whole-cell systems for the bioconversion of ferulic acid into natural equivalent vanillin. The reaction catalysed by HCHL has been thought to proceed by a two-step process involving first the hydration of the double bond of feruloyl-CoA and then the cleavage of the resultant beta-hydroxy thioester by retro-aldol reaction to yield the products. Kinetic analysis of active-site residues identified using the crystal structure of HCHL revealed that while Glu-143 was essential for activity, Ser-123 played no major role in catalysis. However, mutation of Tyr-239 to Phe greatly increased the K(M) for the substrate ferulic acid, fulfilling its anticipated role as a factor in substrate binding. Structures of WT (wild-type) HCHL and of the S123A mutant, each of which had been co-crystallized with feruloyl-CoA, reveal a subtle helix movement upon ligand binding, the consequence of which is to bring the phenolic hydroxyl of Tyr-239 into close proximity to Tyr-75 from a neighbouring subunit in order to bind the phenolic hydroxyl of the product vanillin, for which electron density was observed. The active-site residues of ligand-bound HCHL display a remarkable three-dimensional overlap with those of a structurally unrelated enzyme, vanillyl alcohol oxidase, that also recognizes p-hydroxylated aromatic substrates related to vanillin. The data both explain the observed substrate specificity of HCHL for p-hydroxylated cinnamate derivatives and illustrate a remarkable convergence of the molecular determinants of ligand recognition between the two otherwise unrelated enzymes. A ternary complex of hydroxycinnamoyl-CoA hydratase-lyase (HCHL) with acetyl-CoA and vanillin gives insights into substrate specificity and mechanism.,Bennett JP, Bertin L, Moulton B, Fairlamb IJ, Brzozowski AM, Walton NJ, Grogan G Biochem J. 2008 Sep 1;414(2):281-9. PMID:18479250[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||