S-adenosyl-L-homocysteine hydrolase
Structure of S-adenosylhomocysteine hydrolase from rat liver.[1]
Identifiers
SymbolAd_hcy_hydrolase
PfamPF05221
InterProIPR000043
PROSITEPDOC00603
SCOP21b3r / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1a7a​, 1b3r​, 1d4f​, 1k0u​, 1ky4​, 1ky5​, 1li4​, 1v8b​, 1xwf​
AdoHcyase NAD-binding domain
d244e mutant s-adenosylhomocysteine hydrolase refined with noncrystallographic restraints
Identifiers
SymbolAdoHcyase_NAD
PfamPF00670
Pfam clanCL0063
InterProIPR015878
PROSITEPDOC00603
SCOP21b3r / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

S-adenosyl-L-homocysteine hydrolase (EC 3.3.1.1) (AdoHcyase) is an enzyme of the activated methyl cycle, responsible for the reversible hydration of S-adenosyl-L-homocysteine into adenosine and homocysteine.

AdoHcyase is a ubiquitous enzyme which binds and requires NAD+ as a cofactor. AdoHcyase is a highly conserved protein[2] of 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 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-homocystine (due to equilibrium constant favors S-adenosyl-L-homocystine), a potent inhibitor of methyl transfer reactions.[3]

This protein may use the morpheein model of allosteric regulation.[4]

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. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
This article incorporates text from the public domain Pfam and InterPro: IPR000043
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