2ci6: Difference between revisions
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==Overview== | ==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 .. | 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== | ||
2CI6 is a | 2CI6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. 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] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CI6 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: zinc]] | [[Category: zinc]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 15:16:43 2007'' | ||
Revision as of 16:11, 5 November 2007
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CRYSTAL STRUCTURE OF DIMETHYLARGININE DIMETHYLAMINOHYDROLASE I BOUND WITH ZINC LOW PH
OverviewOverview
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 StructureAbout this Structure
2CI6 is a Single protein structure of sequence from Bos taurus with ZN as ligand. Active as Dimethylargininase, with EC number 3.5.3.18 Structure known Active Site: AC1. Full crystallographic information is available from OCA.
ReferenceReference
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
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