This enzyme belongs to the family of hydrolases, those acting on carbon-nitrogen bonds other than peptide bonds, specifically in cyclic amidines. The systematic name of this enzyme class is adenosine-phosphate aminohydrolase. Other names in common use include adenylate deaminase, adenine nucleotide deaminase, and adenosine (phosphate) deaminase.
The EC number for adenosine-phosphate deaminase is [EC 3.5.4.17].[1] The class is (EC 3) for hydrolase. Hydrolases are enzymes that catalyze bond cleavage by reaction with water.[2] The sub-class refers to adenosine-phosphate deaminase acting on carbon-nitrogen bonds, other than peptide bonds. The sub-sub-class refers to the type of substrate the enzyme is binding to, in this case, cyclic amidines. The final number (17) indicates that adenosine-phosphate deaminase binds to 5'-adenosine monophosphate.[3][4]
Reaction mechanism
The pathway for adenosine-phosphate deaminase involves two substrates, 5'-adenosine monophosphate and water. This pathway is referred to as amidine hydrolysis. Adenosine-phosphate deaminase binds to 5'-AMP using water to break the C-N bond and replacing it with a carbonyl group. Ultimately, this produces 5'-IMP (Inosine monophosphate) and NH3 (ammonia). Substrate specificities of this class depend on their origin, however, all of them deaminate adenosine, 2'-deoxyadenosine, 5'-AMP, and 3',5'-cyclic AMP. Inhibitors of adenosine-phosphate deaminase include Mn2+ (neutral or alkaline pH), F−, Fe3+, CN−, Co2+, Zn2+, and Hg2+.[1][5]
Species distribution
Adenosine-phosphate deaminase is found in most, if not all organisms in all tissues, however, muscle tissue is the richest source.[6] The basic pathway of adenosine-phosphate deaminase is to replace a C-N bond of a 5'-AMP to replace the carboxyl group forming 5'-IMP. 5'-IMP is then catalyzed by Inosine-5'-monophosphate dehydrogenase (IMPDH) in guanine nucleotide biosynthesis. This is at the center of cell growth and proliferation.[7] Specifically within marine mollusks, studies suggest that adenosine-phosphate deaminases are widely distributed across the phylum.[1] However, it was noticed that the pathways varied within each individual species, suggesting that different substrates are preferred within different species.[1] The source organisms for this enzyme are Porphyra crispata, Desulfovibrio desulfuricans, Aspergillus sp..[5]
Function
Within the cell, adenosine-phosphate deaminase is found within all tissues, but particularly higher in concentration within muscle tissue.[6] Kinetic properties of the enzyme vary widely based on the source and purification of the enzyme.[6] Adenosine-phosphate deaminase binds to 5'-AMP performing hydrolysis, using water to break the C-N bond of the amino group attached to 5'-AMP. This results in binding 5'-IMP is then catalyzed by Inosine-5'-monophosphate dehydrogenase (IMPDH), facilitating guanine nucleotide biosynthesis.[7] The initial step of AMP degradation is the conversion to xanthine into alternative routes, xanthosine or hypoxanthine.[8]
Crystal Structure
Molecular weight of adenosine-phosphate deaminase is 30000-60000 Da[5] or 15223 Da.[9] The number of amino acid sequences is 135. There are 0 transmembrane helices.[9]
Active Site
The turnover number for adenosine-phosphate deaminase is 690 ATP, 630 ADP, and 710 AMP. The km value is 0.047 for 5'-AMP. the pH optimum is 6.0-6.8 for 5'-AMP, however the pH range is 4-8 with a temperature optimum of 55 °C.[5] Natural substrates for this enzyme are 5'-AMP and H2O. The substrate spectrum is as follows:[5]
^ abFotie J (2018-04-16). "Inosine 5'-Monophosphate Dehydrogenase (IMPDH) as a Potential Target for the Development of a New Generation of Antiprotozoan Agents". Mini Reviews in Medicinal Chemistry. 18 (8): 656–671. doi:10.2174/1389557516666160620065558. PMID27334467.
Su JC, Li CC, Ting CC (February 1966). "A new adenylate deaminase from red marine alga Porphyra crispata". Biochemistry. 5 (2): 536–543. doi:10.1021/bi00866a020. PMID5940938.
Yates MG (February 1969). "A non-specific adenine nucleotide deaminase from desulfovibrio desulfuricans". Biochimica et Biophysica Acta (BBA) - Enzymology. 171 (2): 299–310. doi:10.1016/0005-2744(69)90163-6. PMID5773435.
