6f97: Difference between revisions

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New page: '''Unreleased structure''' The entry 6f97 is ON HOLD until Paper Publication Authors: Pickl, M., Swoboda, A., Romero, E., Winkler, C.K., Binda, C., Mattevi, A., Faber, K., Fraaije, M.W....
 
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'''Unreleased structure'''


The entry 6f97 is ON HOLD until Paper Publication
==Crystal structure of the V465T mutant of 5-(Hydroxymethyl)furfural Oxidase (HMFO)==
<StructureSection load='6f97' size='340' side='right' caption='[[6f97]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6f97]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mets6 Mets6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6F97 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6F97 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MPQ_0130 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=887061 METS6])</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=6f97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f97 OCA], [http://pdbe.org/6f97 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6f97 RCSB], [http://www.ebi.ac.uk/pdbsum/6f97 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6f97 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/HMFO_METS6 HMFO_METS6]] Involved in the degradation and detoxification of 5-(hydroxymethyl)furfural (HMF) by mediating its oxidation to furan-2,5-dicarboxylate (FDCA), a biobased platform chemical for the production of polymers. Active with a wide range of aromatic and aliphatic primary alcohols and aldehydes: acts on alcohol groups and requires the spontaneous hydration of aldehyde groups for their oxidation (PubMed:24271187, PubMed:24802551). To a lesser extent, is also able to catalyze the oxidation of thiols that are structurally similar to its alcohol substrates, yielding the corresponding thiocarbonyls (PubMed:25284255).<ref>PMID:24271187</ref> <ref>PMID:24802551</ref> <ref>PMID:25284255</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Various flavoprotein oxidases were recently shown to oxidize prim-thiols. Here we extend this reactivity towards sec-thiols via structure-guided engineering of 5-(hydroxymethyl)furfural oxidase (HMFO). The variants obtained were employed for the oxidative kinetic resolution of rac-sec-thiols yielding the correspon notding thioketones and nonreacted (R)-thiols with excellent enantioselectivities (E &gt;/= 200). The engineering strategy applied went beyond the classic approach of replacing bulky amino acid residues with smaller ones, as the active site was additionally enlarged by a newly introduced Thr residue that establishes a hydrogen bonding interaction with the substrates, as predicted by modelling and verified in the crystal structure of the variant. These strategies unlocked HMFO variants for the enantioselective oxidation of a range of sec-thiols.


Authors: Pickl, M., Swoboda, A., Romero, E., Winkler, C.K., Binda, C., Mattevi, A., Faber, K., Fraaije, M.W.
Kinetic Resolution of sec-Thiols via Enantioselective Oxidation with Rationally Engineered 5-(Hydroxymethyl)furfural Oxidase.,Pickl M, Swoboda A, Romero E, Winkler C, Binda C, Mattevi A, Faber K, Fraaije M Angew Chem Int Ed Engl. 2018 Jan 31. doi: 10.1002/anie.201713189. PMID:29384246<ref>PMID:29384246</ref>


Description: Crystal structure of the V465T mutant of 5-(Hydroxymethyl)furfural Oxidase (HMFO)
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Winkler, C.K]]
<div class="pdbe-citations 6f97" style="background-color:#fffaf0;"></div>
[[Category: Romero, E]]
== References ==
[[Category: Fraaije, M.W]]
<references/>
__TOC__
</StructureSection>
[[Category: Mets6]]
[[Category: Binda, C]]
[[Category: Faber, K]]
[[Category: Fraaije, M W]]
[[Category: Mattevi, A]]
[[Category: Mattevi, A]]
[[Category: Faber, K]]
[[Category: Pickl, M]]
[[Category: Pickl, M]]
[[Category: Romero, E]]
[[Category: Swoboda, A]]
[[Category: Swoboda, A]]
[[Category: Binda, C]]
[[Category: Winkler, C K]]
[[Category: Alcohol oxidase]]
[[Category: Biocatalysis]]
[[Category: Enzyme engineering]]
[[Category: Flavoprotein]]
[[Category: Kinetic resolution]]
[[Category: Sec-thiol oxidation]]

Latest revision as of 10:20, 28 February 2018

Crystal structure of the V465T mutant of 5-(Hydroxymethyl)furfural Oxidase (HMFO)Crystal structure of the V465T mutant of 5-(Hydroxymethyl)furfural Oxidase (HMFO)

Structural highlights

6f97 is a 2 chain structure with sequence from Mets6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:MPQ_0130 (METS6)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HMFO_METS6] Involved in the degradation and detoxification of 5-(hydroxymethyl)furfural (HMF) by mediating its oxidation to furan-2,5-dicarboxylate (FDCA), a biobased platform chemical for the production of polymers. Active with a wide range of aromatic and aliphatic primary alcohols and aldehydes: acts on alcohol groups and requires the spontaneous hydration of aldehyde groups for their oxidation (PubMed:24271187, PubMed:24802551). To a lesser extent, is also able to catalyze the oxidation of thiols that are structurally similar to its alcohol substrates, yielding the corresponding thiocarbonyls (PubMed:25284255).[1] [2] [3]

Publication Abstract from PubMed

Various flavoprotein oxidases were recently shown to oxidize prim-thiols. Here we extend this reactivity towards sec-thiols via structure-guided engineering of 5-(hydroxymethyl)furfural oxidase (HMFO). The variants obtained were employed for the oxidative kinetic resolution of rac-sec-thiols yielding the correspon notding thioketones and nonreacted (R)-thiols with excellent enantioselectivities (E >/= 200). The engineering strategy applied went beyond the classic approach of replacing bulky amino acid residues with smaller ones, as the active site was additionally enlarged by a newly introduced Thr residue that establishes a hydrogen bonding interaction with the substrates, as predicted by modelling and verified in the crystal structure of the variant. These strategies unlocked HMFO variants for the enantioselective oxidation of a range of sec-thiols.

Kinetic Resolution of sec-Thiols via Enantioselective Oxidation with Rationally Engineered 5-(Hydroxymethyl)furfural Oxidase.,Pickl M, Swoboda A, Romero E, Winkler C, Binda C, Mattevi A, Faber K, Fraaije M Angew Chem Int Ed Engl. 2018 Jan 31. doi: 10.1002/anie.201713189. PMID:29384246[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Dijkman WP, Fraaije MW. Discovery and characterization of a 5-hydroxymethylfurfural oxidase from Methylovorus sp. strain MP688. Appl Environ Microbiol. 2014 Feb;80(3):1082-90. doi: 10.1128/AEM.03740-13. Epub, 2013 Nov 22. PMID:24271187 doi:http://dx.doi.org/10.1128/AEM.03740-13
  2. ↑ Dijkman WP, Groothuis DE, Fraaije MW. Enzyme-catalyzed oxidation of 5-hydroxymethylfurfural to furan-2,5-dicarboxylic acid. Angew Chem Int Ed Engl. 2014 Jun 16;53(25):6515-8. doi: 10.1002/anie.201402904., Epub 2014 May 6. PMID:24802551 doi:http://dx.doi.org/10.1002/anie.201402904
  3. ↑ Ewing TA, Dijkman WP, Vervoort JM, Fraaije MW, van Berkel WJ. The oxidation of thiols by flavoprotein oxidases: a biocatalytic route to reactive thiocarbonyls. Angew Chem Int Ed Engl. 2014 Nov 24;53(48):13206-9. doi: 10.1002/anie.201407520. , Epub 2014 Oct 5. PMID:25284255 doi:http://dx.doi.org/10.1002/anie.201407520
  4. ↑ Pickl M, Swoboda A, Romero E, Winkler C, Binda C, Mattevi A, Faber K, Fraaije M. Kinetic Resolution of sec-Thiols via Enantioselective Oxidation with Rationally Engineered 5-(Hydroxymethyl)furfural Oxidase. Angew Chem Int Ed Engl. 2018 Jan 31. doi: 10.1002/anie.201713189. PMID:29384246 doi:http://dx.doi.org/10.1002/anie.201713189

6f97, resolution 1.90Å

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