Adenosylhomocysteinase

S-Adenosylhomocysteine hydrolase
SAH hydrolase tetramer, Human
Identifiers
Symbol	AHCY
NCBI gene	191
HGNC	343
OMIM	180960
RefSeq	NM_000687
UniProt	P23526
Other data
EC number	3.3.1.1
Locus	Chr. 20 q11.22
Search for Structures Swiss-model Domains InterPro

S-adenosyl-L-homocysteine hydrolase
Structure of S-adenosylhomocysteine hydrolase from rat liver. [1]
Identifiers
Symbol	Ad_hcy_hydrolase
Pfam	PF05221
InterPro	IPR000043
PROSITE	PDOC00603
SCOP2	1b3r / SCOPe / SUPFAM
Available protein structures: PDB   1a7a ​, 1b3r ​, 1d4f ​, 1k0u ​, 1ky4 ​, 1ky5 ​, 1li4 ​, 1v8b ​, 1xwf ​ IPR000043 PF05221 (ECOD; PDBsum)   AlphaFold IPR000043 PF05221

AdoHcyase NAD-binding domain
d244e mutant s-adenosylhomocysteine hydrolase refined with noncrystallographic restraints
Identifiers
Symbol	AdoHcyase_NAD
Pfam	PF00670
Pfam clan	CL0063
InterPro	IPR015878
PROSITE	PDOC00603
SCOP2	1b3r / SCOPe / SUPFAM
Available protein structures: PDB   IPR015878 PF00670 (ECOD; PDBsum)   AlphaFold IPR015878 PF00670

Adenosylhomocysteinase (EC 3.13.2.1, S-adenosylhomocysteine synthase, S-adenosylhomocysteine hydrolase, adenosylhomocysteine hydrolase, S-adenosylhomocysteinase, SAHase, AdoHcyase) is an enzyme that catalyzes the nicotinamide adenine dinucleotide (NAD⁺) dependent, reversible hydrolysis of S-adenosylhomocysteine to homocysteine and adenosine. ^{[2] [3]}

S-adenosyl-L-homocysteine + H₂O ⇌L-homocysteine + adenosine

AdoHcyase is a highly conserved protein ^[4] with about 430 to 470 amino acids. The family contains a glycine-rich region in the central part of AdoHcyase; a region thought to be involved in NAD-binding. AdoHcyase binds one NAD⁺ cofactor per subunit. This protein may use the morpheein model of allosteric regulation. ^[5]

Overall hydrolysis begins with dehydrogenative oxidation of the 3'-OH of the ribose by NAD⁺ (forming NADH). The resulting ketone is α-deprotonated to the enol before elimination of the homocysteine thiolate. Water then adds to the a,b-unsaturated ketone, before reduction of the resultant ketone by NADH.

AdoHcyase is encoded by the AHCY gene in humans, ^{[6] [7]} which is believed to have a prognostic role in neuroblastoma. ^[8] AdoHcyase is significantly associated with adenosine deaminase deficiency, which classically manifests in severe combine immunodeficiency (SCID). Accumulated adenosine derivatives, dATPs, irreversibly bind to and inhibit AdoHcyase, promoting the buildup of S-adenosyl-L-homocysteine (due to equilibrium constant favors S-adenosyl-L-homocystine), a potent inhibitor of methyl transfer reactions. ^[9]

References

1. Hu Y, Komoto J, Huang Y, et al. (June 1999). "Crystal structure of S-adenosylhomocysteine hydrolase from rat liver". Biochemistry. 38 (26): 8323–33. doi:10.1021/bi990332k. PMID   10387078.
2. De La Haba G, Cantoni GL (March 1959). "The enzymatic synthesis of S-adenosyl-L-homocysteine from adenosine and homocysteine". The Journal of Biological Chemistry. 234 (3): 603–8. doi: 10.1016/S0021-9258(18)70253-6 . PMID   13641268.
3. Palmer JL, Abeles RH (February 1979). "The mechanism of action of S-adenosylhomocysteinase". The Journal of Biological Chemistry. 254 (4): 1217–26. doi: 10.1016/S0021-9258(17)34190-X . PMID   762125.
4. Sganga MW, Aksamit RR, Cantoni GL, Bauer CE (1992). "Mutational and nucleotide sequence analysis of S-adenosyl-L-homocysteine hydrolase from Rhodobacter capsulatus". Proc. Natl. Acad. Sci. U.S.A. 89 (14): 6328–6332. Bibcode:1992PNAS...89.6328S. doi: 10.1073/pnas.89.14.6328 . PMC   49494 . PMID   1631127.
5. T. Selwood; E. K. Jaffe. (2011). "Dynamic dissociating homo-oligomers and the control of protein function". Arch. Biochem. Biophys. 519 (2): 131–43. doi:10.1016/j.abb.2011.11.020. PMC   3298769 . PMID   22182754.
6. GeneCards.org - AHCY Gene - Adenosylhomocysteinase
7. NLM - AHCY adenosylhomocysteinase
8. Chicco, Davide; Sanavia, Tiziana; Jurman, Giuseppe (4 March 2023). "Signature literature review reveals AHCY, DPYSL3, and NME1 as the most recurrent prognostic genes for neuroblastoma". BioData Mining. 16 (1): 7. doi: 10.1186/s13040-023-00325-1 . eISSN   1756-0381. PMC   9985261 . PMID   36870971.
9. Hershfield, M S (1979). "In vivo inactivation of erythrocyte S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine in adenosine deaminase-deficient patients". J Clin Invest. 63 (4): 807–811. doi:10.1172/JCI109367. PMC   372019 . PMID   312296.

External links

• Adenosylhomocysteinase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

Further reading

• Vizán, Pedro; Di Croce, Luciano; Aranda, Sergi (31 March 2021). "Functional and Pathological Roles of AHCY". Frontiers in Cell and Developmental Biology. 9. doi: 10.3389/fcell.2021.654344 . eISSN   2296-634X. PMC   8044520 . PMID   33869213.
• Vugrek, Oliver; Belužić, Robert; Nakić, Nikolina; Mudd, S. Harvey (28 January 2009). "S-adenosylhomocysteine hydrolase (AHCY) deficiency: Two novel mutations with lethal outcome". Human Mutation. 30 (4): E555–E565. doi:10.1002/humu.20985. ISSN   1059-7794. PMC   2876820 . PMID   19177456.

This article incorporates text from the public domain Pfam and InterPro: IPR000043