|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal Structure of dimethylarginine dimethylaminohydrolase I in complex with S-nitroso-Lhomocysteine== | | ==Crystal Structure of dimethylarginine dimethylaminohydrolase I in complex with S-nitroso-Lhomocysteine== |
| - | <StructureSection load='2ci1' size='340' side='right' caption='[[2ci1]], [[Resolution|resolution]] 1.08Å' scene=''> | + | <StructureSection load='2ci1' size='340' side='right'caption='[[2ci1]], [[Resolution|resolution]] 1.08Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ci1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CI1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2CI1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ci1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CI1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CI1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.08Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=K1R:(2S)-2-AMINO-4-[({[(2R)-2-AMINO-2-CARBOXYETHYL]THIO}AMINO)SULFINYL]BUTANOIC+ACID'>K1R</scene>, <scene name='pdbligand=KOR:L-HOMOCYSTEINE-S-N-S-L-CYSTEINE'>KOR</scene>, <scene name='pdbligand=SNC:S-NITROSO-CYSTEINE'>SNC</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=K1R:(2S)-2-AMINO-4-[({[(2R)-2-AMINO-2-CARBOXYETHYL]THIO}AMINO)SULFINYL]BUTANOIC+ACID'>K1R</scene>, <scene name='pdbligand=KOR:L-HOMOCYSTEINE-S-N-S-L-CYSTEINE'>KOR</scene>, <scene name='pdbligand=SNC:S-NITROSO-CYSTEINE'>SNC</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2c6z|2c6z]], [[2ci3|2ci3]], [[2ci4|2ci4]], [[2ci5|2ci5]], [[2ci6|2ci6]], [[2ci7|2ci7]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ci1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ci1 OCA], [https://pdbe.org/2ci1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ci1 RCSB], [https://www.ebi.ac.uk/pdbsum/2ci1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ci1 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ci1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ci1 OCA], [http://pdbe.org/2ci1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ci1 RCSB], [http://www.ebi.ac.uk/pdbsum/2ci1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ci1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DDAH1_BOVIN DDAH1_BOVIN]] Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation. | + | [https://www.uniprot.org/uniprot/DDAH1_BOVIN DDAH1_BOVIN] Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 31: |
Line 29: |
| | </div> | | </div> |
| | <div class="pdbe-citations 2ci1" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2ci1" style="background-color:#fffaf0;"></div> |
| - | | |
| - | ==See Also== | |
| - | *[[Dimethylarginine Dimethylaminohydrolase|Dimethylarginine Dimethylaminohydrolase]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 39: |
Line 34: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Bos taurus]] | | [[Category: Bos taurus]] |
| - | [[Category: Dimethylargininase]] | + | [[Category: Large Structures]] |
| - | [[Category: Braun, O]] | + | [[Category: Braun O]] |
| - | [[Category: Briand, C]] | + | [[Category: Briand C]] |
| - | [[Category: Frey, D]] | + | [[Category: Frey D]] |
| - | [[Category: Grutter, M G]] | + | [[Category: Grutter MG]] |
| - | [[Category: Vasak, M]] | + | [[Category: Vasak M]] |
| - | [[Category: Acetylation]]
| + | |
| - | [[Category: Adma]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Mma]]
| + | |
| - | [[Category: No]]
| + | |
| - | [[Category: Nos regulation]]
| + | |
| - | [[Category: S-nitrosylation]]
| + | |
| - | [[Category: Zinc]]
| + | |
| Structural highlights
Function
DDAH1_BOVIN Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Frey D, Braun O, Briand C, Vasak M, Grutter MG. Structure of the mammalian NOS regulator dimethylarginine dimethylaminohydrolase: A basis for the design of specific inhibitors. Structure. 2006 May;14(5):901-11. PMID:16698551 doi:http://dx.doi.org/10.1016/j.str.2006.03.006
|
