From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1i43.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1i43.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1i43| PDB=1i43 | SCENE= }} | | {{STRUCTURE_1i43| PDB=1i43 | SCENE= }} |
| | | | |
| - | '''CYSTATHIONINE GAMMA-SYNTHASE IN COMPLEX WITH THE INHIBITOR PPCA'''
| + | ===CYSTATHIONINE GAMMA-SYNTHASE IN COMPLEX WITH THE INHIBITOR PPCA=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | Cystathionine gamma-synthase catalyzes the committed step of methionine biosynthesis. This pathway is unique to microorganisms and plants, rendering the enzyme an attractive target for the development of antimicrobials and herbicides. We solved the crystal structures of complexes of cystathionine gamma-synthase (CGS) from Nicotiana tabacum with inhibitors of different compound classes. The complex with the substrate analog dl-E-2-amino-5-phosphono-3-pentenoic acid verifies the carboxylate-binding function of Arg423 and identifies the phosphate-binding pocket of the active site. The structure shows the function of Lys165 in specificity determination and suggests a role for the flexible side-chain of Tyr163 in catalysis. The importance of hydrophobic interactions for binding to the active-site center is highlighted by the complex with 3-(phosphonomethyl)pyridine-2-carboxylic acid. The low affinity of this compound is due to the non-optimal arrangement of the functional groups binding to the phosphate and carboxylate-recognition site, respectively. The newly identified inhibitor 5-carboxymethylthio-3-(3'-chlorophenyl)-1,2,4-oxadiazol, in contrast, shows the highest affinity to CGS reported so far. This affinity is due to binding to an additional active-site pocket not used by the physiological substrates. The inhibitor binds to the carboxylate-recognition site, and its tightly bent conformation enables it to occupy the novel binding pocket between Arg423 and Ser388. The described structures suggest improvements for known inhibitors and give guidelines for the development of new lead compounds.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11518531}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11518531 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_11518531}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 32: |
Line 36: |
| | [[Category: Plp-dependent enzyme]] | | [[Category: Plp-dependent enzyme]] |
| | [[Category: Ppca]] | | [[Category: Ppca]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:32:54 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 10:23:06 2008'' |
Revision as of 07:23, 1 July 2008
Template:STRUCTURE 1i43
CYSTATHIONINE GAMMA-SYNTHASE IN COMPLEX WITH THE INHIBITOR PPCA
Template:ABSTRACT PUBMED 11518531
About this Structure
1I43 is a Single protein structure of sequence from Nicotiana tabacum. Full crystallographic information is available from OCA.
Reference
Crystal structures of cystathionine gamma-synthase inhibitor complexes rationalize the increased affinity of a novel inhibitor., Steegborn C, Laber B, Messerschmidt A, Huber R, Clausen T, J Mol Biol. 2001 Aug 24;311(4):789-801. PMID:11518531
Page seeded by OCA on Tue Jul 1 10:23:06 2008
