Biology:Adenosine-phosphate deaminase
| adenosine-phosphate deaminase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 3.5.4.17 | ||||||||
| CAS number | 37289-20-6 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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In enzymology, an adenosine-phosphate deaminase (EC 3.5.4.17) is an enzyme that catalyzes the chemical reaction
- 5'-AMP + H2O [math]\displaystyle{ \rightleftharpoons }[/math] 5'-IMP + NH3
Thus, the two substrates of this enzyme are 5'-AMP and H2O, whereas its two products are 5'-IMP and NH3.
Classification
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]
Adenosine + H2O
Adenosine phosphates + H2O
NAD+ + H2O
dATP + H2O
dADP + H2O
dAMP + H2O
Deoxyadenosine + H2O
The product spectrum is as follows:[5]
Inosine + NH3
Inosine phosphates + NH3
Nicotinamide-hypoxanthine-dinucleotide + NH3
dITP + NH3
dIDP + NH3
dIMP + NH3
Deoxyinosine + NH3
References
- ↑ 1.0 1.1 1.2 1.3 "Purification and Some Properties of Adenosine (Phosphate) Deaminase from the Liver of the Squid Todarodes pacificus" (in en). Bioscience, Biotechnology, and Biochemistry 59 (7): 1276–1280. January 1995. doi:10.1271/bbb.59.1276. ISSN 0916-8451. https://academic.oup.com/bbb/article/59/7/1276-1280/5951590.
- ↑ (in English) Hydrolases in Organic Synthesis: Regio- and Stereoselective Biotransformatics (2nd ed.). Wiley-Blackwell. 2006. pp. 1. ISBN 978-3-527-60712-9.
- ↑ "EC 3.5.4". https://iubmb.qmul.ac.uk/enzyme/EC3/5/4/.
- ↑ "EC 3.5.4.17". https://iubmb.qmul.ac.uk/enzyme/EC3/5/4/17.html.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 (in English) Enzyme Handbook 4. Springer. 1991. pp. 1059–1062. ISBN 978-3-642-84437-9.
- ↑ 6.0 6.1 6.2 "Univalent cations as allosteric activators of muscle adenosine 5'-phosphate deaminase". The Journal of Biological Chemistry 242 (8): 1980–1981. April 1967. doi:10.1016/S0021-9258(18)96097-7. PMID 6024785.
- ↑ 7.0 7.1 "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. 2018-04-16. doi:10.2174/1389557516666160620065558. PMID 27334467.
- ↑ "MetaCyc Reaction: 3.5.4.6/3.5.4.17". 1 March 2012. https://biocyc.org/META/new-image?object=AMP-DEAMINASE-RXN.
- ↑ 9.0 9.1 "Information on EC 3.5.4.17 - adenosine-phosphate deaminase - BRENDA Enzyme Database". https://www.brenda-enzymes.org/enzyme.php?ecno=3.5.4.17#UNIPROT.
Further reading
- "A new adenylate deaminase from red marine alga Porphyra crispata". Biochemistry 5 (2): 536–543. February 1966. doi:10.1021/bi00866a020. PMID 5940938.
- "A non-specific adenine nucleotide deaminase from desulfovibrio desulfuricans". Biochimica et Biophysica Acta (BBA) - Enzymology 171 (2): 299–310. February 1969. doi:10.1016/0005-2744(69)90163-6. PMID 5773435.
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