title: Crystal structure of HINT from Helicobacter pylori.
abstract: Proteins belonging to the histidine triad (HIT) superfamily bind nucleotides and use the histidine triad motif to carry out dinucleotidyl hydrolase, nucleotidyltransferase and phosphoramidite hydrolase activities. Five different branches of this superfamily are known to exist. Defects in these proteins in humans are linked to many diseases such as ataxia, diseases of RNA metabolism and cell-cycle regulation, and various types of cancer. The histidine triad nucleotide protein (HINT) is nearly identical to proteins that have been classified as protein kinase C-interacting proteins (PKCIs), which also have the ability to bind and inhibit protein kinase C. The structure of HINT, which exists as a homodimer, is highly conserved from humans to bacteria and shares homology with the product of fragile histidine triad protein (FHit), a tumour suppressor gene of this superfamily. Here, the structure of HINT from Helicobacter pylori (HpHINT) in complex with AMP is reported at a resolution of 3 Å. The final model has R and Rfree values of 26 and 28%, respectively, with good electron density. Structural comparison with previously reported homologues and phylogenetic analysis shows H. pylori HINT to be the smallest among them, and suggests that it branched out separately during the course of evolution. Overall, this structure has contributed to a better understanding of this protein across the animal kingdom.
authors.affiliation: School of Life Science, Jawaharlal Nehru University, New Delhi, Delhi 110 067, India.
authors.forename: K F
authors.initials: KF
authors.lastname: Tarique
authors.affiliation: School of Life Science, Jawaharlal Nehru University, New Delhi, Delhi 110 067, India.
authors.forename: S
authors.initials: S
authors.lastname: Devi
authors.affiliation: School of Life Science, Jawaharlal Nehru University, New Delhi, Delhi 110 067, India.
authors.forename: S A
authors.initials: SA
authors.lastname: Abdul Rehman
authors.affiliation: School of Life Science, Jawaharlal Nehru University, New Delhi, Delhi 110 067, India.
authors.forename: S
authors.initials: S
authors.lastname: Gourinath
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000737:chemistry*; D000249:Adenosine Monophosphate / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D016480:Helicobacter pylori / Q000201:enzymology*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D040681:Structural Homology, Protein
chemical_list: D001426:Bacterial Proteins; D000249:Adenosine Monophosphate; D017766:Acid Anhydride Hydrolases
keywords: Helicobacter pylori; cell cycle; crystal structure; histidine trinucleotide repeat; protein kinase C-interacting protein