Adenosylhomocysteinase
Protein-coding gene in the species Homo sapiens
From Wikipedia, the free encyclopedia
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-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 | ||||||
| |||||||
| 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 | ||||||
| |||||||
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]
