2vss: Difference between revisions

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==Wild-type Hydroxycinnamoyl-CoA hydratase lyase in complex with acetyl- CoA and vanillin==
The line below this paragraph, containing "STRUCTURE_2vss", creates the "Structure Box" on the page.
<StructureSection load='2vss' size='340' side='right'caption='[[2vss]], [[Resolution|resolution]] 2.22&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<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>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.22&#8491;</td></tr>
-->
<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>
{{STRUCTURE_2vss|  PDB=2vss  |  SCENE=  }}
<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>
</table>
== 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 ==
[[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/vs/2vss_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=2vss ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
HCHL (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.


'''WILD-TYPE HYDROXYCINNAMOYL-COA HYDRATASE LYASE IN COMPLEX WITH ACETYL-COA AND VANILLIN'''
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<ref>PMID:18479250</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==Overview==
</div>
Hydroxycinnamoyl-CoA Hydratase-Lyase (HCHL) 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 to 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, 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 whilst Glu-143 was essential for activity, Ser-123 played no major role in catalysis. However, mutation of Tyr-239 to Phe greatly increased the KM for the substrate ferulic acid, fulfilling its anticipated role as a factor in substrate binding. Structures of wild-type HCHL and of the Ser123Ala mutant, each of which had been co-crystallised 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 with 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 recognises para-hydroxylated aromatic substrates related to vanillin. The data both explain the observed substrate specificity of HCHL for para-hydroxylated cinnamate derivatives and illustrate a remarkable convergence of the molecular determinants of ligand recognition between two otherwise unrelated enzymes.
<div class="pdbe-citations 2vss" style="background-color:#fffaf0;"></div>
 
== References ==
==About this Structure==
<references/>
2VSS is a [[Single protein]] structure of sequence from [http://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].
__TOC__
 
</StructureSection>
==Reference==
[[Category: Large Structures]]
A ternary complex of Hydroxycinnamoyl-CoA Hydratase-Lyase (HCHL) with acetyl-Coenzyme A 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 May 14;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18479250 18479250]
[[Category: Pseudomonas fluorescens]]
[[Category: Pseudomonas fluorescens]]
[[Category: Single protein]]
[[Category: Bennett JP]]
[[Category: Trans-feruloyl-CoA hydratase]]
[[Category: Bertin LM]]
[[Category: Bennett, J P.]]
[[Category: Brzozowski AM]]
[[Category: Bertin, L M.]]
[[Category: Grogan G]]
[[Category: Brzozowski, A M.]]
[[Category: Walton NJ]]
[[Category: Grogan, G.]]
[[Category: Walton, N J.]]
[[Category: Aldolase]]
[[Category: Crotonase]]
[[Category: Hydratase]]
[[Category: Lyase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 28 09:16:57 2008''

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

2vss is a 6 chain structure with sequence from Pseudomonas fluorescens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.22Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).[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 PubMed

HCHL (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

  1. ↑ Gasson MJ, Kitamura Y, McLauchlan WR, Narbad A, Parr AJ, Parsons EL, Payne J, Rhodes MJ, Walton NJ. Metabolism of ferulic acid to vanillin. A bacterial gene of the enoyl-SCoA hydratase/isomerase superfamily encodes an enzyme for the hydration and cleavage of a hydroxycinnamic acid SCoA thioester. J Biol Chem. 1998 Feb 13;273(7):4163-70. PMID:9461612
  2. ↑ Bennett JP, Bertin L, Moulton B, Fairlamb IJ, Brzozowski AM, Walton NJ, Grogan G. A ternary complex of hydroxycinnamoyl-CoA hydratase-lyase (HCHL) with acetyl-CoA and vanillin gives insights into substrate specificity and mechanism. Biochem J. 2008 Sep 1;414(2):281-9. PMID:18479250 doi:10.1042/BJ20080714

2vss, resolution 2.22Å

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