Bacterial PhyA protein-tyrosine phosphatase-like myo-inositol phosphatases in complex with the Ins(1,3,4,5)P4 and Ins(1,4,5)P3 second messengers.

摘要: myo-Inositol phosphates (IPs) are important bioactive molecules that have multiple activities within eukaryotic cells, including well-known roles as second messengers and cofactors help regulate diverse biochemical processes such transcription hormone receptor activity. Despite the typical absence of IPs in prokaryotes, many these organisms express IPases (or phytases) dephosphorylate IPs. Functionally, enzymes participate phosphate-scavenging pathways plant pathogenesis. Here, we determined X-ray crystallographic structures two catalytically inactive mutants protein-tyrosine phosphatase-like myo-inositol phosphatases (PTPLPs) from non-pathogenic bacteria Selenomonas ruminantium (PhyAsr) Mitsuokella multacida (PhyAmm) complex with known Ins(1,3,4,5)P4 Ins(1,4,5)P3. Both bound less-phosphorylated a competent manner, suggesting IP hydrolysis has role The binding differed both ring position orientation when compared previously structure presence myo-inositol-1,2,3,4,5,6-hexakisphosphate (InsP6 or phytate). Further, demonstrated PhyAsr PhyAmm different specificities for Ins(1,2,4,5,6)P5, identified structural features account this difference, shown results broad specificity toward Ins(1,2,4,5,6)P5. These main-chain conformational differences loops adjacent to active site include extended loop prior penultimate helix, Ω-loop, β-hairpin turn Phy-specific domain.