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| | <StructureSection load='6szq' size='340' side='right'caption='[[6szq]], [[Resolution|resolution]] 2.41Å' scene=''> | | <StructureSection load='6szq' size='340' side='right'caption='[[6szq]], [[Resolution|resolution]] 2.41Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6szq]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SZQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SZQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6szq]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SZQ FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DDAH1, DDAH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 2.412Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=6szq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6szq OCA], [https://pdbe.org/6szq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6szq RCSB], [https://www.ebi.ac.uk/pdbsum/6szq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6szq ProSAT]</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=6szq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6szq OCA], [http://pdbe.org/6szq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6szq RCSB], [http://www.ebi.ac.uk/pdbsum/6szq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6szq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DDAH1_HUMAN DDAH1_HUMAN]] 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_HUMAN DDAH1_HUMAN] 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dimethylargininase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hennig, S]] | + | [[Category: Hennig S]] |
| - | [[Category: Schade, D]] | + | [[Category: Schade D]] |
| - | [[Category: Vetter, I R]] | + | [[Category: Vetter IR]] |
| - | [[Category: Dimethylarginine dimethylaminohydrolase]]
| + | |
| - | [[Category: Guanidine inhibitor]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Induced fit]]
| + | |
| - | [[Category: Prodrug]]
| + | |
| Structural highlights
Function
DDAH1_HUMAN 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.
Publication Abstract from PubMed
N-(4-aminobutyl)-N'-(2-methoxyethyl)guanidine (8a) is as a potent inhibitor targeting the hDDAH-1 active site (Ki = 18 microM) and derived from a series of guanidine- and amidine-based inhibitors. Its non-amino acid nature leads to high selectivities towards other enzymes of the nitric oxide-modulating system. Crystallographic data of 8a-bound hDDAH-1 illuminated a unique binding mode. Together with its developed N-hydroxyguanidine prodrug 11, 8a will serve as a most widely applicable, currently available pharmacological tool to target DDAH-1-associated diseases.
Discovery of N-(4-Aminobutyl)-N'-(2-Methoxyethyl)guanidine as the First Selective, Non-Amino Acid, Catalytic Site Inhibitor of human dimethylarginine dimethylaminohydrolase-1 (hDDAH-1).,Lunk I, Litty FA, Hennig S, Vetter IR, Kotthaus J, Altmann KS, Ott G, Havemeyer A, Carrillo Garcia C, Clement B, Schade D J Med Chem. 2019 Dec 16. doi: 10.1021/acs.jmedchem.9b01230. PMID:31841335[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lunk I, Litty FA, Hennig S, Vetter IR, Kotthaus J, Altmann KS, Ott G, Havemeyer A, Carrillo Garcia C, Clement B, Schade D. Discovery of N-(4-Aminobutyl)-N'-(2-Methoxyethyl)guanidine as the First Selective, Non-Amino Acid, Catalytic Site Inhibitor of human dimethylarginine dimethylaminohydrolase-1 (hDDAH-1). J Med Chem. 2019 Dec 16. doi: 10.1021/acs.jmedchem.9b01230. PMID:31841335 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b01230
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