N(G),N(G)-dimethylarginine dimethylaminohydrolase 2
| Basic Information | |
|---|---|
| Short Name | DDAH2 |
| UNP ID | O95865 |
| Organism | Homo sapiens |
| Cys Site | Cys276 |
| Family/Domain | DDAH family |
| Known Ligand | Ligand list |
| Function Type | Metabolic enzyme |
Summary
Protein Function
In the field of enzymology, a dimethylargininase, also known as a dimethylarginine dimethylaminohydrolase (DDAH), is an enzyme that catalyzes the chemical reaction:
DDAH is an enzyme found in all mammalian cells. Two isoforms exist, DDAH I and DDAH II, with some differences in tissue distribution of the two isoforms. The enzyme degrades methylarginines, specifically asymmetric dimethylarginine (ADMA) and NG-monomethyl-L-arginine (MMA).
The methylarginines ADMA and MMA inhibit the production of nitric oxide synthase. As such, DDAH is important in removing methylarginines, generated by protein degradation, from accumulating and inhibiting the generation of nitric oxide. (From Wikipedia)
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. (From Uniprot)
Cys Function & Property
Cys276 is one of the active site of DDAH1, which act as the nucleophile group in catalyze.
- Hydrophobic property:
- SASA：
- Cys276: Unknown
Protein Sequence
MGTPGEGLGR CSHALIRGVP ESLASGEGAG AGLPALDLAK AQREHGVLGG
KLRQRLGLQL LELPPEESLP LGPLLGDTAV IQGDTALITR PWSPARRPEV
DGVRKALQDL GLRIVEIGDE NATLDGTDVL FTGREFFVGL SKWTNHRGAE
IVADTFRDFA VSTVPVSGPS HLRGLCGMGG PRTVVAGSSD AAQKAVRAMA
VLTDHPYASL TLPDDAAADC LFLRPGLPGV PPFLLHRGGG DLPNSQEALQ
KLSDVTLVPV SCSELEKAGA GLSSLCLVLS TRPHS
Structural Information
- Known structure with covalent ligand:
- Unknown
- Protein structure:
- Unknown
Related Pathway
- Unknown
Experimental Evidence
- Homologous Analysis of Sequence, Molecular Docking
Reference
- Wang Y, Monzingo A F, Hu S, et al. Developing dual and specific inhibitors of dimethylarginine dimethylaminohydrolase-1 and nitric oxide synthase: toward a targeted polypharmacology to control nitric oxide[J]. Biochemistry, 2009, 48(36): 8624-8635. 19663506
- Linsky T W, Fast W. Discovery of structurally-diverse inhibitor scaffolds by high-throughput screening of a fragment library with dimethylarginine dimethylaminohydrolase[J]. Bioorganic & medicinal chemistry, 2012, 20(18): 5550-5558. 22921743
