1t5f
From Proteopedia
(New page: 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=" | + | [[Image:1t5f.gif|left|200px]]<br /><applet load="1t5f" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1t5f, resolution 2.20Å" /> | caption="1t5f, resolution 2.20Å" /> | ||
'''arginase I-AOH complex'''<br /> | '''arginase I-AOH complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Arginase is a binuclear manganese metalloenzyme that catalyzes the | + | 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:// | + | 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 | + | [[Category: Christianson, D W.]] |
[[Category: Shin, H.]] | [[Category: Shin, H.]] | ||
[[Category: DHH]] | [[Category: DHH]] | ||
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[[Category: arginase]] | [[Category: arginase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:10:03 2008'' |
Revision as of 13:10, 21 February 2008
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arginase I-AOH complex
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.
About this Structure
1T5F is a Single protein structure of sequence from Rattus norvegicus with and as ligands. Active as Arginase, with EC number 3.5.3.1 Full crystallographic information is available from OCA.
Reference
Design of amino acid aldehydes as transition-state analogue inhibitors of arginase., Shin H, Cama E, Christianson DW, J Am Chem Soc. 2004 Aug 25;126(33):10278-84. PMID:15315440
Page seeded by OCA on Thu Feb 21 15:10:03 2008
Categories: Arginase | Rattus norvegicus | Single protein | Cama, E. | Christianson, D W. | Shin, H. | DHH | MN | Aoh
