4yar

From Proteopedia

(Difference between revisions)

Revision as of 11:21, 4 March 2015

2-Hydroxyethylphosphonate dioxygenase (HEPD) E176H

Structural highlights

4yar is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Activity:	2-hydroxyethylphosphonate dioxygenase, with EC number 1.13.11.72
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[HEPD_STRVR] Non-heme-dependent dioxygenase that catalyzes the conversion of 2-hydroxyethylphosphonate (HEP) to hydroxymethylphosphonate (HMP) in the biosynthesis of phosphinothricin tripeptide (PTT). PTT contains the unusual amino acid phosphinothricin attached to 2 alanine residues. Synthetic phosphinothricin (glufosinate) is a key component of commercial herbicides.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

2-Hydroxyethylphosphonate dioxygenase (HEPD) and methylphosphonate synthase (MPnS) are nonheme iron oxygenases that both catalyze the carbon-carbon bond cleavage of 2-hydroxyethylphosphonate but generate different products. Substrate labeling experiments led to a mechanistic hypothesis in which the fate of a common intermediate determined product identity. We report here the generation of a bifunctional mutant of HEPD (E176H) that exhibits the activity of both HEPD and MPnS. The product distribution of the mutant is sensitive to a substrate isotope effect, consistent with an isotope-sensitive branching mechanism involving a common intermediate. The X-ray structure of the mutant was determined and suggested that the introduced histidine does not coordinate the active site metal, unlike the iron-binding glutamate it replaced.

A Common Late-Stage Intermediate in Catalysis by 2-Hydroxyethyl-phosphonate Dioxygenase and Methylphosphonate Synthase.,Peck SC, Chekan JR, Ulrich EC, Nair SK, van der Donk WA J Am Chem Soc. 2015 Feb 26. PMID:25699631^[6]

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

References

↑ Blodgett JA, Thomas PM, Li G, Velasquez JE, van der Donk WA, Kelleher NL, Metcalf WW. Unusual transformations in the biosynthesis of the antibiotic phosphinothricin tripeptide. Nat Chem Biol. 2007 Aug;3(8):480-5. Epub 2007 Jul 15. PMID:17632514 doi:http://dx.doi.org/10.1038/nchembio.2007.9
↑ Cicchillo RM, Zhang H, Blodgett JA, Whitteck JT, Li G, Nair SK, van der Donk WA, Metcalf WW. An unusual carbon-carbon bond cleavage reaction during phosphinothricin biosynthesis. Nature. 2009 Jun 11;459(7248):871-4. PMID:19516340 doi:10.1038/nature07972
↑ Whitteck JT, Cicchillo RM, van der Donk WA. Hydroperoxylation by hydroxyethylphosphonate dioxygenase. J Am Chem Soc. 2009 Nov 11;131(44):16225-32. doi: 10.1021/ja906238r. PMID:19839620 doi:http://dx.doi.org/10.1021/ja906238r
↑ Whitteck JT, Malova P, Peck SC, Cicchillo RM, Hammerschmidt F, van der Donk WA. On the stereochemistry of 2-hydroxyethylphosphonate dioxygenase. J Am Chem Soc. 2011 Mar 30;133(12):4236-9. doi: 10.1021/ja1113326. Epub 2011 Mar , 7. PMID:21381767 doi:http://dx.doi.org/10.1021/ja1113326
↑ Peck SC, Cooke HA, Cicchillo RM, Malova P, Hammerschmidt F, Nair SK, van der Donk WA. Mechanism and Substrate Recognition of 2-Hydroxyethylphosphonate Dioxygenase. Biochemistry. 2011 Jul 8. PMID:21711001 doi:10.1021/bi200804r
↑ Peck SC, Chekan JR, Ulrich EC, Nair SK, van der Donk WA. A Common Late-Stage Intermediate in Catalysis by 2-Hydroxyethyl-phosphonate Dioxygenase and Methylphosphonate Synthase. J Am Chem Soc. 2015 Feb 26. PMID:25699631 doi:http://dx.doi.org/10.1021/jacs.5b00282

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4yar"

Categories: 2-hydroxyethylphosphonate dioxygenase | Chekan, J R | Nair, S K | Dioxygenase

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==2-Hydroxyethylphosphonate dioxygenase (HEPD) E176H==
+<StructureSection load='4yar' size='340' side='right' caption='[[4yar]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4yar]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YAR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YAR FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2-hydroxyethylphosphonate_dioxygenase 2-hydroxyethylphosphonate dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.72 1.13.11.72] </span></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=4yar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yar OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yar RCSB], [http://www.ebi.ac.uk/pdbsum/4yar PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/HEPD_STRVR HEPD_STRVR]] Non-heme-dependent dioxygenase that catalyzes the conversion of 2-hydroxyethylphosphonate (HEP) to hydroxymethylphosphonate (HMP) in the biosynthesis of phosphinothricin tripeptide (PTT). PTT contains the unusual amino acid phosphinothricin attached to 2 alanine residues. Synthetic phosphinothricin (glufosinate) is a key component of commercial herbicides.<ref>PMID:17632514</ref> <ref>PMID:19516340</ref> <ref>PMID:19839620</ref> <ref>PMID:21381767</ref> <ref>PMID:21711001</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+-Hydroxyethylphosphonate dioxygenase (HEPD) and methylphosphonate synthase (MPnS) are nonheme iron oxygenases that both catalyze the carbon-carbon bond cleavage of 2-hydroxyethylphosphonate but generate different products. Substrate labeling experiments led to a mechanistic hypothesis in which the fate of a common intermediate determined product identity. We report here the generation of a bifunctional mutant of HEPD (E176H) that exhibits the activity of both HEPD and MPnS. The product distribution of the mutant is sensitive to a substrate isotope effect, consistent with an isotope-sensitive branching mechanism involving a common intermediate. The X-ray structure of the mutant was determined and suggested that the introduced histidine does not coordinate the active site metal, unlike the iron-binding glutamate it replaced.
-The entry 4yar is ON HOLD  until Paper Publication
+A Common Late-Stage Intermediate in Catalysis by 2-Hydroxyethyl-phosphonate Dioxygenase and Methylphosphonate Synthase.,Peck SC, Chekan JR, Ulrich EC, Nair SK, van der Donk WA J Am Chem Soc. 2015 Feb 26. PMID:25699631<ref>PMID:25699631</ref>
-Authors: Chekan, J.R., Nair, S.K.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: 2-Hydroxyethylphosphonate dioxygenase (HEPD) E176H
+== References ==
-[[Category: Unreleased Structures]]
+<references/>
-[[Category: Nair, S.K]]
+__TOC__
-[[Category: Chekan, J.R]]
+</StructureSection>
+[[Category: 2-hydroxyethylphosphonate dioxygenase]]
+[[Category: Chekan, J R]]
+[[Category: Nair, S K]]
+[[Category: Dioxygenase]]

4yar

From Proteopedia

Revision as of 11:21, 4 March 2015

2-Hydroxyethylphosphonate dioxygenase (HEPD) E176H

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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