View source for N(G),N(G)-dimethylarginine dimethylaminohydrolase 1

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{{#invoke:InfoboxforTarget|run|DDAH1|[https://www.uniprot.org/uniprot/O94760 O94760]|Homo sapiens|Cys274|DDAH family|[[:Category:N(G),N(G)-dimethylarginine dimethylaminohydrolase 1|Ligand list]]|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: <br/>
<div align="center">N-omega,N-omega'-methyl-L-arginine + H2O ↔ dimethylamine + L-citrulline</div>
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).<br/>
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)<br/>
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)<br/>

===Cys Function & Property===
Cys274 is one of the active site of DDAH1, which act as the nucleophile group in catalyze.<br/>

* Hydrophobic property:
:[[File:558-hydro.png||600px]]
* SASA：
:Cys274: 7.407 A^2 <br/>

==Protein Sequence==
<font face="Courier">
MAGLGHPAAF GRATHAVVRA LPESLGQHAL RSAKGEEVDV ARAERQHQLY <br/>
VGVLGSKLGL QVVELPADES LPDCVFVEDV AVVCEETALI TRPGAPSRRK <br/>
EVDMMKEALE KLQLNIVEMK DENATLDGGD VLFTGREFFV GLSKRTNQRG <br/>
AEILADTFKD YAVSTVPVAD GLHLKSFCSM AGPNLIAIGS SESAQKALKI <br/>
MQQMSDHRYD KLTVPDDIAA NCIYLNIPNK GHVLLHRTPE EYPESAKVYE <br/>
KLKDHMLIPV SMSELEKVDG LLT<span style="background:#ffff00">'''C'''</span>CSVLIN KKVDS       <br/> 
</font>

==Structural Information==
*Known structure with covalent ligand: <br/>
:[https://www.rcsb.org/structure/3I4A 3I4A], [https://www.rcsb.org/structure/3P8P 3P8P], [https://www.rcsb.org/structure/3P8E 3P8E]<br/>  

*Protein structure:
:[[File:558.png|center|800px]]

==Related Pathway==
:Unknown <br/>

==Experimental Evidence==
:Crystallography, 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. [https://www.ncbi.nlm.nih.gov/pubmed/?term=19663506 19663506]<br/> 
# Lluis M, Wang Y, Monzingo A F, et al. '''Characterization of C‐Alkyl Amidines as Bioavailable Covalent Reversible Inhibitors of Human DDAH‐1[J].''' ChemMedChem, 2011, 6(1): 81-88. [https://www.ncbi.nlm.nih.gov/pubmed/?term=20979083 20979083]<br/> 
# 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. [https://www.ncbi.nlm.nih.gov/pubmed/?term=22921743 22921743]<br/> 

[[Category:Targets|Targets]]
[[Category:Homo sapiens|Homo sapiens]]
[[Category:Metabolic enzyme|Metabolic enzyme]]
[[Category:DDAH family|DDAH family]]