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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1a4l

E.C. nameadenosine deaminase
SpeciesMus musculus (Mouse)
E.C. Number (IntEnz) 3.5.4.4
CSA Homologues of 1a4lThere are 28 Homologs
CSA Entries With UniProtID P03958
CSA Entries With EC Number 3.5.4.4
PDBe Entry 1a4l
PDBSum Entry 1a4l
MACiE Entry 1a4l

Literature Report

IntroductionAdenosine deaminase (ADA) is the critical enzyme in purine metabolism, which catalyses the irreversible deamination of adenosine and deoxyadenosine to their respective inosine product. It is present in virtually all mammalian cells and has a central role in maintaining immune competence. Genetic deficiency of ADA in humans is associated with severe combined immunodeficiency disease, whereas abnormally high level of ADA is involved in a variety of other diseases including acquired immunodeficiency syndrome (AIDS), tuberculosis, Parkinson's disease, anemia, various lymphomas and leukemias. ADA is therefore regarded as an important therapeutic target and the detailed knowledge of its catalytic mechanism is of high significance in drug design.
MechansimADA catalyses the irreversible hydrolytic deamination of adenosine nucleosides to inosine nucleosides and ammonia. The reaction has two stages – nucleophilic addition of water to the substrate, and elimination of ammonia from the intermediate.
Reaction

Catalytic Sites for 1a4l

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA217217macie:sideChainDeprotonates water and donates the proton to N1 on the substrate.
HisA238238macie:sideChainAssists formation and stabilisation of the attacking hydroxide. Shuttles proton from Zn-coordinated hydroxyl to 6-NH2.
AspA295295macie:sideChainEnsures correct stereochemistry of the hydroxide addition.

Literature References

Notes:
Kahata K
Inhaled vancomycin-induced allergic reaction in decontamination of respiratory tracts for allogeneic bone marrow transplantation.
Bone Marrow Transplant 1997 20 1001-1003
PubMed: 9422483
Wu XH
A theoretical study on the catalytic mechanism of Mus musculus adenosine deaminase.
J Comput Chem 2010 31 2238-2247
PubMed: 20575011
Wang Z
Complexes of adenosine deaminase with two potent inhibitors: X-ray structures in four independent molecules at pH of maximum activity.
Biochemistry 1998 37 8314-8324
PubMed: 9622483
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