2ci4
From Proteopedia
(New page: 200px<br /><applet load="2ci4" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ci4, resolution 1.70Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:2ci4.gif|left|200px]]<br /><applet load="2ci4" size=" | + | [[Image:2ci4.gif|left|200px]]<br /><applet load="2ci4" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2ci4, resolution 1.70Å" /> | caption="2ci4, resolution 1.70Å" /> | ||
'''CRYSTAL STRUCTURE OF DIMETHYLARGININE DIMETHYLAMINOHYDROLASE I CRYSTAL FORM II'''<br /> | '''CRYSTAL STRUCTURE OF DIMETHYLARGININE DIMETHYLAMINOHYDROLASE I CRYSTAL FORM II'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Dimethylarginine dimethylaminohydrolase (DDAH) is involved in the | + | Dimethylarginine dimethylaminohydrolase (DDAH) is involved in the regulation of nitric oxide synthase (NOS) by metabolizing the free endogenous arginine derivatives N(omega)-methyl-L-arginine (MMA) and N(omega),N(omega)-dimethyl-L-arginine (ADMA), which are competitive inhibitors of NOS. Here, we present high-resolution crystal structures of DDAH isoform 1 (DDAH-1) isolated from bovine brain in complex with different inhibitors, including S-nitroso-L-homocysteine and Zn2+, a regulator of this mammalian enzyme. The structure of DDAH-1 consists of a propeller-like fold similar to other arginine-modifying enzymes and a flexible loop, which adopts different conformations and acts as a lid at the entrance of the active site. The orientation and interaction mode of inhibitors in the active site give insight into the regulation and the molecular mechanism of the enzyme. The presented structures provide a basis for the structure-based development of specific DDAH-1 inhibitors that might be useful in the therapeutic treatment of NOS dysfunction-related diseases. |
==About this Structure== | ==About this Structure== | ||
| - | 2CI4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Active as [http://en.wikipedia.org/wiki/Dimethylargininase Dimethylargininase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.18 3.5.3.18] Full crystallographic information is available from [http:// | + | 2CI4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Active as [http://en.wikipedia.org/wiki/Dimethylargininase Dimethylargininase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.18 3.5.3.18] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CI4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Briand, C.]] | [[Category: Briand, C.]] | ||
[[Category: Frey, D.]] | [[Category: Frey, D.]] | ||
| - | [[Category: Grutter, M | + | [[Category: Grutter, M G.]] |
[[Category: Vasak, M.]] | [[Category: Vasak, M.]] | ||
[[Category: acetylation]] | [[Category: acetylation]] | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:48:52 2008'' |
Revision as of 14:48, 21 February 2008
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CRYSTAL STRUCTURE OF DIMETHYLARGININE DIMETHYLAMINOHYDROLASE I CRYSTAL FORM II
Overview
Dimethylarginine dimethylaminohydrolase (DDAH) is involved in the regulation of nitric oxide synthase (NOS) by metabolizing the free endogenous arginine derivatives N(omega)-methyl-L-arginine (MMA) and N(omega),N(omega)-dimethyl-L-arginine (ADMA), which are competitive inhibitors of NOS. Here, we present high-resolution crystal structures of DDAH isoform 1 (DDAH-1) isolated from bovine brain in complex with different inhibitors, including S-nitroso-L-homocysteine and Zn2+, a regulator of this mammalian enzyme. The structure of DDAH-1 consists of a propeller-like fold similar to other arginine-modifying enzymes and a flexible loop, which adopts different conformations and acts as a lid at the entrance of the active site. The orientation and interaction mode of inhibitors in the active site give insight into the regulation and the molecular mechanism of the enzyme. The presented structures provide a basis for the structure-based development of specific DDAH-1 inhibitors that might be useful in the therapeutic treatment of NOS dysfunction-related diseases.
About this Structure
2CI4 is a Single protein structure of sequence from Bos taurus. Active as Dimethylargininase, with EC number 3.5.3.18 Full crystallographic information is available from OCA.
Reference
Structure of the mammalian NOS regulator dimethylarginine dimethylaminohydrolase: A basis for the design of specific inhibitors., Frey D, Braun O, Briand C, Vasak M, Grutter MG, Structure. 2006 May;14(5):901-11. PMID:16698551
Page seeded by OCA on Thu Feb 21 16:48:52 2008
Categories: Bos taurus | Dimethylargininase | Single protein | Braun, O. | Briand, C. | Frey, D. | Grutter, M G. | Vasak, M. | Acetylation | Adma | Hydrolase | Metal-binding | Mma | No | Nos regulation | S-nitrosylation | Zinc
