Adenosylhomocysteinase

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

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: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB 1a7a​, 1b3r​, 1d4f​, 1k0u​, 1ky4​, 1ky5​, 1li4​, 1v8b​, 1xwf​

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: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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]