4yar: Difference between revisions

Latest revision as of 07:55, 27 September 2023

2-Hydroxyethylphosphonate dioxygenase (HEPD) E176H

Structural highlights

4yar is a 1 chain structure with sequence from Streptomyces viridochromogenes. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.75Å
Ligands:	ACT, CD, NA
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HEPD_STRVT 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:https://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:https://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:https://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:https://dx.doi.org/10.1021/jacs.5b00282

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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:https://dx.doi.org/10.1038/nchembio.2007.9

[2] 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

[3] 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:https://dx.doi.org/10.1021/ja906238r

[4] 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:https://dx.doi.org/10.1021/ja1113326

[5] 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

[6] 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:https://dx.doi.org/10.1021/jacs.5b00282

[1]

[2]

[3]

[4]

[5]

[6]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 4yar is ON HOLD  until Paper Publication
+==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 with sequence from [https://en.wikipedia.org/wiki/Streptomyces_viridochromogenes Streptomyces viridochromogenes]. 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 [https://proteopedia.org/fgij/fg.htm?mol=4YAR 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]] 1.75&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4yar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yar OCA], [https://pdbe.org/4yar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yar RCSB], [https://www.ebi.ac.uk/pdbsum/4yar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yar ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/HEPD_STRVT HEPD_STRVT] 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.
-Authors: Chekan, J.R., Nair, S.K.
+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>
-Description: 2-Hydroxyethylphosphonate dioxygenase (HEPD) E176H
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Nair, S.K]]
+<div class="pdbe-citations 4yar" style="background-color:#fffaf0;"></div>
-[[Category: Chekan, J.R]]
+==See Also==
+*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Streptomyces viridochromogenes]]
+[[Category: Chekan JR]]
+[[Category: Nair SK]]

4yar: Difference between revisions

Latest revision as of 07:55, 27 September 2023

2-Hydroxyethylphosphonate dioxygenase (HEPD) E176H

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools