1t4t: Difference between revisions

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[[Image:1t4t.gif|left|200px]]
{{Seed}}
[[Image:1t4t.png|left|200px]]


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{{STRUCTURE_1t4t|  PDB=1t4t  |  SCENE=  }}  
{{STRUCTURE_1t4t|  PDB=1t4t  |  SCENE=  }}  


'''arginase-dinor-NOHA complex'''
===arginase-dinor-NOHA complex===




==Overview==
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Arginase is a manganese metalloenzyme that catalyzes the hydrolysis of L-arginine to form L-ornithine and urea. The structure and stability of the binuclear manganese cluster are critical for catalytic activity as it activates the catalytic nucleophile, metal-bridging hydroxide ion, and stabilizes the tetrahedral intermediate and its flanking states. Here, we report X-ray structures of a series of inhibitors bound to the active site of arginase, and each inhibitor exploits a different mode of coordination with the Mn(2+)(2) cluster. Specifically, we have studied the binding of fluoride ion (F(-); an uncompetitive inhibitor) and L-arginine, L-valine, dinor-N(omega)-hydroxy-L-arginine, descarboxy-nor-N(omega)-hydroxy-L-arginine, and dehydro-2(S)-amino-6-boronohexanoic acid. Some inhibitors, such as fluoride ion, dinor-N(omega)-hydroxy-L-arginine, and dehydro-2(S)-amino-6-boronohexanoic acid, cause the net addition of one ligand to the Mn(2+)(2) cluster. Other inhibitors, such as descarboxy-nor-N(omega)-hydroxy-L-arginine, simply displace the metal-bridging hydroxide ion of the native enzyme and do not cause any net change in the metal coordination polyhedra. The highest affinity inhibitors displace the metal-bridging hydroxide ion (and sometimes occupy a Mn(2+)(A) site found vacant in the native enzyme) and maintain a conserved array of hydrogen bonds with their alpha-amino and -carboxylate groups.
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{{ABSTRACT_PUBMED_15248756}}


==About this Structure==
==About this Structure==
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[[Category: Arginase]]
[[Category: Arginase]]
[[Category: Dinor-noha]]
[[Category: Dinor-noha]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 09:31:46 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 11:02:59 2008''

Revision as of 08:03, 28 July 2008

File:1t4t.png

Template:STRUCTURE 1t4t

arginase-dinor-NOHA complex

Template:ABSTRACT PUBMED 15248756

About this Structure

1T4T is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

Inhibitor coordination interactions in the binuclear manganese cluster of arginase., Cama E, Pethe S, Boucher JL, Han S, Emig FA, Ash DE, Viola RE, Mansuy D, Christianson DW, Biochemistry. 2004 Jul 20;43(28):8987-99. PMID:15248756

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