1t5f: Difference between revisions

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New page: left|200px<br /><applet load="1t5f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t5f, resolution 2.20Å" /> '''arginase I-AOH compl...
 
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[[Image:1t5f.gif|left|200px]]<br /><applet load="1t5f" size="450" color="white" frame="true" align="right" spinBox="true"  
[[Image:1t5f.gif|left|200px]]<br /><applet load="1t5f" size="350" color="white" frame="true" align="right" spinBox="true"  
caption="1t5f, resolution 2.20&Aring;" />
caption="1t5f, resolution 2.20&Aring;" />
'''arginase I-AOH complex'''<br />
'''arginase I-AOH complex'''<br />


==Overview==
==Overview==
Arginase is a binuclear manganese metalloenzyme that catalyzes the, hydrolysis of l-arginine to form l-ornithine and urea. Chiral L-amino, acids bearing aldehyde side chains have been synthesized in which the, electrophilic aldehyde C=O bond is isosteric with the C=N bond of, L-arginine. This substitution is intended to facilitate nucleophilic, attack by the metal-bridging hydroxide ion upon binding to the arginase, active site. Syntheses of the amino acid aldehydes have been accomplished, by reduction, oxidation, and Wittig-type reaction with a commercially, available derivative of L-glutamic acid. Amino acid aldehydes exhibit, inhibition in the micromolar range, and the X-ray crystal structure of, arginase I complexed with one of these inhibitors, (S)-2-amino-7-oxoheptanoic acid, has been determined at 2.2 A resolution., In the enzyme-inhibitor complex, the inhibitor aldehyde moiety is hydrated, to form the gem-diol: one hydroxyl group bridges the Mn(2+)(2) cluster and, donates a hydrogen bond to D128, and the second hydroxyl group donates a, hydrogen bond to E277. The binding mode of the neutral gem-diol may mimic, the binding of the neutral tetrahedral intermediate and its flanking, transition states in arginase catalysis.
Arginase is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea. Chiral L-amino acids bearing aldehyde side chains have been synthesized in which the electrophilic aldehyde C=O bond is isosteric with the C=N bond of L-arginine. This substitution is intended to facilitate nucleophilic attack by the metal-bridging hydroxide ion upon binding to the arginase active site. Syntheses of the amino acid aldehydes have been accomplished by reduction, oxidation, and Wittig-type reaction with a commercially available derivative of L-glutamic acid. Amino acid aldehydes exhibit inhibition in the micromolar range, and the X-ray crystal structure of arginase I complexed with one of these inhibitors, (S)-2-amino-7-oxoheptanoic acid, has been determined at 2.2 A resolution. In the enzyme-inhibitor complex, the inhibitor aldehyde moiety is hydrated to form the gem-diol: one hydroxyl group bridges the Mn(2+)(2) cluster and donates a hydrogen bond to D128, and the second hydroxyl group donates a hydrogen bond to E277. The binding mode of the neutral gem-diol may mimic the binding of the neutral tetrahedral intermediate and its flanking transition states in arginase catalysis.


==About this Structure==
==About this Structure==
1T5F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with MN and DHH as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Arginase Arginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.1 3.5.3.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1T5F OCA].  
1T5F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=MN:'>MN</scene> and <scene name='pdbligand=DHH:'>DHH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Arginase Arginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.1 3.5.3.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T5F OCA].  


==Reference==
==Reference==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Cama, E.]]
[[Category: Cama, E.]]
[[Category: Christianson, D.W.]]
[[Category: Christianson, D W.]]
[[Category: Shin, H.]]
[[Category: Shin, H.]]
[[Category: DHH]]
[[Category: DHH]]
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[[Category: arginase]]
[[Category: arginase]]


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