1p8s
From Proteopedia
(New page: 200px<br /><applet load="1p8s" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p8s, resolution 3.20Å" /> '''Structural and Funct...) |
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| - | [[Image:1p8s.gif|left|200px]]<br /><applet load="1p8s" size=" | + | [[Image:1p8s.gif|left|200px]]<br /><applet load="1p8s" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1p8s, resolution 3.20Å" /> | caption="1p8s, resolution 3.20Å" /> | ||
'''Structural and Functional Importance of First-Shell Metal Ligands in the Binuclear Manganese Cluster of Arginase I.'''<br /> | '''Structural and Functional Importance of First-Shell Metal Ligands in the Binuclear Manganese Cluster of Arginase I.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Arginase is a binuclear manganese metalloenzyme that hydrolyzes l-arginine | + | Arginase is a binuclear manganese metalloenzyme that hydrolyzes l-arginine to form l-ornithine and urea. The three-dimensional structures of D128E, D128N, D232A, D232C, D234E, H101N, and H101E arginases I have been determined by X-ray crystallographic methods to elucidate the roles of the first-shell metal ligands in the stability and catalytic activity of the enzyme. This work represents the first structure-based dissection of the binuclear manganese cluster using site-directed mutagenesis and X-ray crystallography. Substitution of the metal ligands compromises the catalytic activity of the enzyme, either by the loss or disruption of the metal cluster or the nucleophilic metal-bridging hydroxide ion. However, the substitution of the metal ligands or the reduction of Mn(2+)(A) or Mn(2+)(B) occupancy does not compromise enzyme-substrate affinity as reflected by K(M), which remains relatively invariant across this series of arginase variants. This implicates a nonmetal binding site for substrate l-arginine in the precatalytic Michaelis complex, as proposed based on analysis of the native enzyme structure (Kanyo, Z. F., Scolnick, L. R., Ash, D. E., and Christianson, D. W. (1996) Nature 383, 554-557). |
==About this Structure== | ==About this Structure== | ||
| - | 1P8S 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 as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | + | 1P8S 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> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1P8S OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Ash, D | + | [[Category: Ash, D E.]] |
[[Category: Cama, E.]] | [[Category: Cama, E.]] | ||
| - | [[Category: Christianson, D | + | [[Category: Christianson, D W.]] |
| - | [[Category: Emig, F | + | [[Category: Emig, F A.]] |
[[Category: MN]] | [[Category: MN]] | ||
[[Category: arginine metabolism]] | [[Category: arginine metabolism]] | ||
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[[Category: urea cycle]] | [[Category: urea cycle]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:26:23 2008'' |
Revision as of 12:26, 21 February 2008
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Structural and Functional Importance of First-Shell Metal Ligands in the Binuclear Manganese Cluster of Arginase I.
Overview
Arginase is a binuclear manganese metalloenzyme that hydrolyzes l-arginine to form l-ornithine and urea. The three-dimensional structures of D128E, D128N, D232A, D232C, D234E, H101N, and H101E arginases I have been determined by X-ray crystallographic methods to elucidate the roles of the first-shell metal ligands in the stability and catalytic activity of the enzyme. This work represents the first structure-based dissection of the binuclear manganese cluster using site-directed mutagenesis and X-ray crystallography. Substitution of the metal ligands compromises the catalytic activity of the enzyme, either by the loss or disruption of the metal cluster or the nucleophilic metal-bridging hydroxide ion. However, the substitution of the metal ligands or the reduction of Mn(2+)(A) or Mn(2+)(B) occupancy does not compromise enzyme-substrate affinity as reflected by K(M), which remains relatively invariant across this series of arginase variants. This implicates a nonmetal binding site for substrate l-arginine in the precatalytic Michaelis complex, as proposed based on analysis of the native enzyme structure (Kanyo, Z. F., Scolnick, L. R., Ash, D. E., and Christianson, D. W. (1996) Nature 383, 554-557).
About this Structure
1P8S is a Single protein structure of sequence from Rattus norvegicus with as ligand. Active as Arginase, with EC number 3.5.3.1 Full crystallographic information is available from OCA.
Reference
Structural and functional importance of first-shell metal ligands in the binuclear manganese cluster of arginase I., Cama E, Emig FA, Ash DE, Christianson DW, Biochemistry. 2003 Jul 1;42(25):7748-58. PMID:12820884
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