Adenosine-phosphate deaminase

In enzymology, an adenosine-phosphate deaminase (EC 3.5.4.17) is an enzyme that catalyzes the chemical reaction

adenosine-phosphate deaminase
Identifiers
EC no.3.5.4.17
CAS no.37289-20-6
Databases
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KEGGKEGG entry
MetaCycmetabolic pathway
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5'-AMP + H2O 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

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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

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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

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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

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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

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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

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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

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  1. ^ a b c d Uchida H, Narita Y, Masuda A, Matsui Y, Chen YX, Takahashi I, Maeda S, Nomura A (January 1995). "Purification and Some Properties of Adenosine (Phosphate) Deaminase from the Liver of the Squid Todarodes pacificus". Bioscience, Biotechnology, and Biochemistry. 59 (7): 1276–1280. doi:10.1271/bbb.59.1276. ISSN 0916-8451.
  2. ^ Bornscheuer UT, Kazlauskas RJ (2006). Hydrolases in Organic Synthesis: Regio- and Stereoselective Biotransformatics (2nd ed.). Wiley-Blackwell. p. 1. ISBN 978-3-527-60712-9.
  3. ^ "EC 3.5.4". iubmb.qmul.ac.uk. Retrieved 2022-10-21.
  4. ^ "EC 3.5.4.17". iubmb.qmul.ac.uk. Retrieved 2022-10-21.
  5. ^ a b c d e f Schomburg D, Salzmann M (1991). Enzyme Handbook 4. Springer. pp. 1059–1062. ISBN 978-3-642-84437-9.
  6. ^ a b c Smiley KL, Suelter CH (April 1967). "Univalent cations as allosteric activators of muscle adenosine 5'-phosphate deaminase". The Journal of Biological Chemistry. 242 (8): 1980–1981. doi:10.1016/S0021-9258(18)96097-7. PMID 6024785.
  7. ^ a b Fotie 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. PMID 27334467.
  8. ^ "MetaCyc Reaction: 3.5.4.6/3.5.4.17". Biocyc.org. 1 March 2012.
  9. ^ a b "Information on EC 3.5.4.17 - adenosine-phosphate deaminase - BRENDA Enzyme Database". www.brenda-enzymes.org. Retrieved 2022-10-21.

Further reading

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  • 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. PMID 5940938.
  • 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. PMID 5773435.