1v4g
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1v4g.gif|left|200px]] | [[Image:1v4g.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1v4g", 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_1v4g| PDB=1v4g | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal Structure of gamma-Glutamylcysteine Synthetase from Escherichia coli B''' | '''Crystal Structure of gamma-Glutamylcysteine Synthetase from Escherichia coli B''' | ||
| Line 32: | Line 29: | ||
[[Category: Nii, H.]] | [[Category: Nii, H.]] | ||
[[Category: Oda, J.]] | [[Category: Oda, J.]] | ||
| - | [[Category: | + | [[Category: Beta barrel]] |
| - | [[Category: | + | [[Category: Glutathione regulation]] |
| - | [[Category: | + | [[Category: Peptide synthesis]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 12:03:54 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 09:03, 3 May 2008
Crystal Structure of gamma-Glutamylcysteine Synthetase from Escherichia coli B
Overview
Gamma-glutamylcysteine synthetase (gammaGCS), a rate-limiting enzyme in glutathione biosynthesis, plays a central role in glutathione homeostasis and is a target for development of potential therapeutic agents against parasites and cancer. We have determined the crystal structures of Escherichia coli gammaGCS unliganded and complexed with a sulfoximine-based transition-state analog inhibitor at resolutions of 2.5 and 2.1 A, respectively. In the crystal structure of the complex, the bound inhibitor is phosphorylated at the sulfoximido nitrogen and is coordinated to three Mg2+ ions. The cysteine-binding site was identified; it is formed inductively at the transition state. In the unliganded structure, an open space exists around the representative cysteine-binding site and is probably responsible for the competitive binding of glutathione. Upon inhibitor binding, the side chains of Tyr-241 and Tyr-300 turn, forming a hydrogen-bonding triad with the carboxyl group of the inhibitor's cysteine moiety, allowing this moiety to fit tightly into the cysteine-binding site with concomitant accommodation of its side chain into a shallow pocket. This movement is caused by a conformational change of a switch loop (residues 240-249). Based on this crystal structure, the cysteine-binding sites of mammalian and parasitic gammaGCSs were predicted by multiple sequence alignment, although no significant sequence identity exists between the E. coli gammaGCS and its eukaryotic homologues. The identification of this cysteine-binding site provides important information for the rational design of novel gammaGCS inhibitors.
About this Structure
1V4G is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Crystal structure of gamma-glutamylcysteine synthetase: insights into the mechanism of catalysis by a key enzyme for glutathione homeostasis., Hibi T, Nii H, Nakatsu T, Kimura A, Kato H, Hiratake J, Oda J, Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15052-7. Epub 2004 Oct 11. PMID:15477603 Page seeded by OCA on Sat May 3 12:03:54 2008
