2d33: 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:2d33.gif|left|200px]]
{{Seed}}
[[Image:2d33.png|left|200px]]


<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2d33|  PDB=2d33  |  SCENE=  }}  
{{STRUCTURE_2d33|  PDB=2d33  |  SCENE=  }}  


'''Crystal Structure of gamma-Glutamylcysteine Synthetase Complexed with Aluminum Fluoride'''
===Crystal Structure of gamma-Glutamylcysteine Synthetase Complexed with Aluminum Fluoride===


==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==
==About this Structure==
2D33 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D33 OCA].  
2D33 is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2D33 OCA].  


==Reference==
==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:[http://www.ncbi.nlm.nih.gov/pubmed/15477603 15477603]
<ref group="xtra">PMID:15477603</ref><ref group="xtra">PMID:11807262</ref><references group="xtra"/>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Glutamate--cysteine ligase]]
[[Category: Glutamate--cysteine ligase]]
[[Category: Single protein]]
[[Category: Hibi, T.]]
[[Category: Hibi, T.]]
[[Category: Katano, H.]]
[[Category: Katano, H.]]
Line 32: Line 29:
[[Category: Peptide synthesis]]
[[Category: Peptide synthesis]]
[[Category: Phosphoryl transfer]]
[[Category: Phosphoryl transfer]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 23:36:29 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 21:35:15 2009''

Revision as of 19:35, 16 February 2009

File:2d33.png

Template:STRUCTURE 2d33

Crystal Structure of gamma-Glutamylcysteine Synthetase Complexed with Aluminum Fluoride

About this Structure

2D33 is a 4 chains structure of sequences from Escherichia coli. Full crystallographic information is available from OCA.

Reference

  1. Hibi T, Nii H, Nakatsu T, Kimura A, Kato H, Hiratake J, Oda J. Crystal structure of gamma-glutamylcysteine synthetase: insights into the mechanism of catalysis by a key enzyme for glutathione homeostasis. Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15052-7. Epub 2004 Oct 11. PMID:15477603
  2. Hibi T, Hisada H, Nakatsu T, Kato H, Oda J. Escherichia coli B gamma-glutamylcysteine synthetase: modification, purification, crystallization and preliminary crystallographic analysis. Acta Crystallogr D Biol Crystallogr. 2002 Feb;58(Pt 2):316-8. Epub 2002, Jan 24. PMID:11807262

Page seeded by OCA on Mon Feb 16 21:35:15 2009

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=2d33&oldid=854321"