Conformational changes in inositol 1,3,4,5,6-pentakisphosphate 2-kinase upon substrate binding: role of N-terminal lobe and enantiomeric substrate preference.

ABSTRACT: Inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IP(5) 2-K) catalyzes the synthesis of inositol 1,2,3,4,5,6-hexakisphosphate from ATP and IP(5). Inositol 1,2,3,4,5,6-hexakisphosphate is implicated in crucial processes such as mRNA export, DNA editing, and phosphorus storage in plants. We previously solved the first structure of an IP(5) 2-K, which shed light on aspects of substrate recognition. However, failure of IP(5) 2-K to crystallize in the absence of inositide prompted us to study putative conformational changes upon substrate binding. We have made mutations to residues on a region of the protein that produces a clasp over the active site. A W129A mutant allowed us to capture IP(5) 2-K in its different conformations by crystallography. Thus, the IP(5) 2-K apo-form structure displays an

SUBMITTER: Banos-Sanz JI 

PROVIDER: S-EPMC3436203 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature