Crystal structure of HINT fromHelicobacter 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.

Response toErrors in Crystal structure of HINT from Helicobacter pylori

“…We appreciate and thank Ms Maize for showing interest in our article (Tarique et al, 2016), for writing such a comprehensive critique in her Letter to the Editor (Maize, 2016), and also for raising this issue in the general interest of the scientific community.…”

“…As HINT and PKCI are the same then, in our opinion, we prefer not to use the term PKCI at all, even though it is used continually in other places. In the manuscript by Tarique et al (2016) both old and new references were used and it was inferred that HINT and PKCI are different proteins but with very similar structure. However, we are thankful to Ms Maize who has raised and resolved this issue.…”