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Catalytic Site Atlas

CSA LITERATURE entry for 5fit

E.C. namebis(5'-adenosyl)-triphosphatase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 3.6.1.29
CSA Homologues of 5fitThere are 23 Homologs
CSA Entries With UniProtID P49789
CSA Entries With EC Number 3.6.1.29
PDBe Entry 5fit
PDBSum Entry 5fit
MACiE Entry M0101

Literature Report

Introduction The FHIT protein is a diadenosine P1, P3-triphosphate (ApppA) hydrolase that cleaves diadenosine P1, P3-triphosphate to yield AMP and ADP which is found in animals and fungi. In humans the FHIT gene is found at 3p14.2 and is thought to act as a tumour suppressor gene involved in many human cancers. It belongs to one branch of the Histidine triad (HIT) superfamily of nucleotide-binding proteins which have a conserved His-X-His-X-His-X-X (where X is a hydrophobic amino acid) motif. This was originally thought to be a zinc-ion binding site but is now believed to be the alpha-phosphate binding site [SEE REF:1]. The other branch of this superfamily consists of the HINT (histidine triad nucleotide-binding) proteins, the proposed ancestor of FHIT, galactose-1-phosphate uridylyltransferase, and other nucleotide binding proteins [SEE REF:1].
Mechansim A catalytic mechanism for FHIT proteins (and possibly other members of the HIT superfamily) has been proposed [see REF: 2]. Histidine96 is activated as a nucleophile by Histidine94 so that the ND1 atom can attack the alpha phosphate group of the substrate as it enters the binding pocket. This causes the inversion of the alpha phosphate position to form a trigonal bipyramidal pentacovalent transition state from which the products are formed either by hydrolysis or transfer of the phosphoramidate bond.
Reaction

Catalytic Sites for 5fit

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlnA8383macie:sideChain
HisA9696macie:sideChain
HisA9494macie:sideChain

Literature References

Notes: 2fit and 3fit are classified as 'Chromosomal Translocation' and 'Complex (Chromosomal Translocation Ade)' respectively in the PDB rather than 'Hydrolase' as the rest of EC 3.6.1.29 are. Therefore they are not listed under EC3.6.1.29, but are FHIT structures.
Brenner C
Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins.
Nat Struct Biol 1997 4 231-238
PubMed: 9164465
Lima CD
Structure-based analysis of catalysis and substrate definition in the HIT protein family.
Science 1997 278 286-290
PubMed: 9323207
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