1i48
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1i48.gif|left|200px]] | [[Image:1i48.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1i48", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1i48| PDB=1i48 | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''CYSTATHIONINE GAMMA-SYNTHASE IN COMPLEX WITH THE INHIBITOR CTCPO''' | '''CYSTATHIONINE GAMMA-SYNTHASE IN COMPLEX WITH THE INHIBITOR CTCPO''' | ||
| Line 31: | Line 28: | ||
[[Category: Messerschmidt, A.]] | [[Category: Messerschmidt, A.]] | ||
[[Category: Steegborn, C.]] | [[Category: Steegborn, C.]] | ||
| - | [[Category: | + | [[Category: Ctcpo]] |
| - | [[Category: | + | [[Category: Homotetramer]] |
| - | [[Category: | + | [[Category: Inhibitor complex]] |
| - | [[Category: | + | [[Category: Plp-dependent enzyme]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:33:12 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 16:33, 2 May 2008
CYSTATHIONINE GAMMA-SYNTHASE IN COMPLEX WITH THE INHIBITOR CTCPO
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.
About this Structure
1I48 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 Fri May 2 19:33:12 2008
