2pqd: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
Line 1: Line 1:
[[Image:2pqd.jpg|left|200px]]
{{Seed}}
[[Image:2pqd.png|left|200px]]


<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2pqd|  PDB=2pqd  |  SCENE=  }}  
{{STRUCTURE_2pqd|  PDB=2pqd  |  SCENE=  }}  


'''A100G CP4 EPSPS liganded with (R)-difluoromethyl tetrahedral reaction intermediate analog'''
===A100G CP4 EPSPS liganded with (R)-difluoromethyl tetrahedral reaction intermediate analog===




==Overview==
<!--
The shikimate pathway enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSP synthase or EPSPS) is best known as the target of the herbicide glyphosate. EPSPS is also considered an attractive target for the development of novel antibiotics since the pathogenicity of many microorganisms depends on the functionality of the shikimate pathway. Here, we have investigated the inhibitory potency of stable fluorinated or phosphonate-based analogues of the tetrahedral reaction intermediate (TI) in a parallel study utilizing class I (glyphosate-sensitive) and class II (glyphosate-tolerant) EPSPS. The (R)-difluoromethyl and (R)-phosphonate analogues of the TI are the most potent inhibitors of EPSPS described to date. However, we found that class II EPSPS are up to 400 times less sensitive to inhibition by these TI analogues. X-ray crystallographic data revealed that the conformational changes of active site residues observed upon inhibitor binding to the representative class I EPSPS from Escherichia coli do not occur in the prototypical class II enzyme from Agrobacterium sp. strain CP4. It appears that because the active sites of class II EPSPS do not possess the flexibility to accommodate these TI analogues, the analogues themselves undergo conformational changes, resulting in less favorable inhibitory properties. Since pathogenic microorganisms such as Staphylococcus aureus utilize class II EPSPS, we conclude that the rational design of novel EPSPS inhibitors with potential as broad-spectrum antibiotics should be based on the active site structures of class II EPSP synthases.
The line below this paragraph, {{ABSTRACT_PUBMED_17958399}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 17958399 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_17958399}}


==About this Structure==
==About this Structure==
Line 29: Line 33:
[[Category: Inside-out alpha/beta barrel]]
[[Category: Inside-out alpha/beta barrel]]
[[Category: Transferase]]
[[Category: Transferase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 13:37:43 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 13:52:08 2008''

Revision as of 10:52, 29 July 2008

File:2pqd.png

Template:STRUCTURE 2pqd

A100G CP4 EPSPS liganded with (R)-difluoromethyl tetrahedral reaction intermediate analog

Template:ABSTRACT PUBMED 17958399

About this Structure

2PQD is a Single protein structure of sequence from Agrobacterium sp.. Full crystallographic information is available from OCA.

Reference

Differential inhibition of class I and class II 5-enolpyruvylshikimate-3-phosphate synthases by tetrahedral reaction intermediate analogues., Funke T, Healy-Fried ML, Han H, Alberg DG, Bartlett PA, Schonbrunn E, Biochemistry. 2007 Nov 20;46(46):13344-51. Epub 2007 Oct 25. PMID:17958399

Page seeded by OCA on Tue Jul 29 13:52:08 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=2pqd&oldid=743967"