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320  structures 6336  species 0  interactions 14475  sequences 69  architectures

Family: AdoHcyase (PF05221)

Summary: S-adenosyl-L-homocysteine hydrolase

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This is the Wikipedia entry entitled "S-adenosyl-L-homocysteine hydrolase". More...

S-adenosyl-L-homocysteine hydrolase Edit Wikipedia article

S-adenosyl-L-homocysteine hydrolase
PDB 1b3r EBI.jpg
Structure of S-adenosylhomocysteine hydrolase from rat liver.[1]
AdoHcyase NAD-binding domain
PDB 1ky5 EBI.jpg
d244e mutant s-adenosylhomocysteine hydrolase refined with noncrystallographic restraints
Pfam clanCL0063

S-adenosyl-L-homocysteine hydrolase (EC (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]


  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/ PMC 3298769. PMID 22182754.
This article incorporates text from the public domain Pfam and InterPro: IPR000043

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000043

Adenosylhomocysteinase (S-adenosyl-L-homocysteine hydrolase, EC ) (AdoHcyase) is an enzyme of the activated methyl cycle, responsible for the reversible hydration of S-adenosyl-L-homocysteine into adenosine and homocysteine. This enzyme is ubiquitous, highly conserved, and may play a key role in the regulation of the intracellular concentration of adenosylhomocysteine. AdoHcyase requires NAD+ as a cofactor and contains a central glycine-rich region which is thought to be involved in NAD-binding. Since AdoHyc is a potent inhibitor of S-adenosyl-L-methionine dependent methyltransferases, AdoHycase plays a critical role in the modulation of the activity of various methyltransferases. The enzyme forms homotetramers, with each monomer binding one molecule of NAD+ [ PUBMED:9586999 , PUBMED:16061414 , PUBMED:11325033 , PUBMED:15165742 ].

This family also includes S-adenosylhomocysteine hydrolase-like 1 (Ahcyl1), also known as IRBIT, and S-adenosylhomocysteine hydrolase-like protein 2 (Ahcyl2). Ahcyl1/IRBIT was shown to interact with inositol 1,4,5-trisphosphate receptors (IP3Rs), which function as intracellular Ca(2+) channels, and suppresses IP3 binding of IP3R [ PUBMED:16793548 , PUBMED:16527252 ]. By competing with IP3, it modulates the threshold IP3 concentration required for the activation of the receptor [ PUBMED:16793548 ]. Further studies indicate that Ahcyl1/IRBIT is in fact a multifunctional protein that regulates several ion channels and ion transporters [ PUBMED:24518248 , PUBMED:21152975 ]. Despite its homology to S-adenosylhomocysteine hydrolases, Ahcyl1 has neither enzyme activity nor any effects on the enzyme activity of S-adenosylhomocysteine hydrolase [ PUBMED:12525476 ]. Ahcyl2 lacks binding activity to IP3R [ PUBMED:19220705 ]. Ahcyl2 upregulates NBCe1-B, which plays an important role in intracellular pH regulation [ PUBMED:27382360 ].

Domain organisation

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Pfam Clan

This family is a member of clan Form_Glyc_dh (CL0325), which has the following description:

This superfamily includes the catalytic domain of a variety of dehydrogenase enzymes. The domain has a flavodoxin-like fold and contains an inserted Rossman fold NAD-binding domain.

The clan contains the following 4 members:

2-Hacid_dh AdoHcyase AlaDh_PNT_N DpaA_N


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Seed source: Pfam-B_157 (release 2.1)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 144
Number in full: 14475
Average length of the domain: 275.60 aa
Average identity of full alignment: 36 %
Average coverage of the sequence by the domain: 93.84 %

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HMM build commands:
build method: hmmbuild -o /dev/null --hand HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 25.3 25.0
Noise cut-off 24.5 24.9
Model length: 299
Family (HMM) version: 19
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Species distribution

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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the AdoHcyase domain has been found. There are 320 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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