Sandbox Reserved 1058: Difference between revisions

Dimethylarginine Dimethyaminohydrolase <span class="plainlinks">[http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/5/3/18.html EC 3.5.3.18]</span> (commonly known as DDAH) is a member of the <span class="plainlinks">[https://en.wikipedia.org/wiki/Hydrolase hydrolase]</span> family of enzymes which use water to break down molecules <ref name="palm">Palm F, Onozato ML, Luo Z, Wilcox CS. Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems. American Journal of Physiology. 2007 Dec 1;293(6):3227-3245. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/17933965 17933965]</span> doi:<span class="plainlinks">[http://ajpheart.physiology.org/content/293/6/H3227 10.1152/ajpheart.00998.2007]</span></ref>. Additionally, DDAH is a <span class="plainlinks">[https://en.wikipedia.org/wiki/Nitric_oxide_synthase nitric oxide synthase (NOS)]</span> regulator. It metabolizes free arginine derivatives, namely <span class="plainlinks">[https://en.wikipedia.org/wiki/Asymmetric_dimethylarginine N^Ѡ,N^Ѡ-dimethyl-L-arginine (ADMA)]</span> and <span class="plainlinks">[https://en.wikipedia.org/wiki/Methylarginine N^Ѡ-methyl-L-arginine (MMA)]</span>, which competitively inhibit NOS <ref name="tran">Tran CTL, Leiper JM, Vallance P. The DDAH/ADMA/NOS pathway. Atherosclerosis Supplements. 2003 Dec;4(4):33-40. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/14664901 14664901]</span> doi:<span class="plainlinks">[http://www.sciencedirect.com/science/article/pii/S1567568803000321 10.1016/S1567-5688(03)00032-1]</span></ref>. DDAH converts MMA or ADMA to two products: <span class="plainlinks">[https://en.wikipedia.org/wiki/Citrulline L-citrulline]</span> and an amine <ref name="frey">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):901-911. PMID:<span class="plainlinks">[https://www.ncbi.nlm.nih.gov/pubmed/16698551]</span> doi:<span class="plainlinks">[http://www.sciencedirect.com/science/article/pii/S0969212606001717 10.1016/j.str.2006.03.006]</span></ref> (Figure 1). DDAH is expressed in the cytosol of cells in humans, mice, rats, sheep, cattle, and bacteria <ref name="palm" />. DDAH activity has been localized mainly to the brain, kidneys, pancreas, and liver in these organisms. Presented in this page is information from DDAH isoform 1 (DDAH-1); however, there are two different isoforms <ref name="frey" />.

The specific residues in the lid region vary between organisms <ref name="frey" /> (Figure 2). The only consistent similarity is a <span class="plainlinks">[https://en.wikipedia.org/wiki/Conserved_sequence conserved]</span> leucine residue in this lid that functions to hydrogen bond with the <span class="plainlinks">[https://en.wikipedia.org/wiki/Ligand ligand]</span> bound to the active site in DDAH-1 but not in DDAH-2 <ref name="rasheed" /> (Figure 2). Different <span class="plainlinks">[https://en.wikipedia.org/wiki/Protein_isoform isoforms]</span> from the same species can have differences in lid regions as well <ref name="frey" />. DDAH-2 has a negatively charged lid while DDAH-1 has a positively charged lid <ref name="frey" />.

[[Image:Lid Region WebLogo.png|500 px|center|thumb|'''Figure 2.''' WebLogo for the lid region in DDAH-1 of eight different organisms.]]