Deprotonation states of the two active site water molecules regulate the binding of protein phosphatase 5 with its substrate: A molecular dynamics study.

ABSTRACT: Protein phosphatase 5 (PP5), mainly localized in human brain, can dephosphorylate tau protein whose high level of phosphorylation is related to Alzheimer's disease. Similar to other protein phosphatases, PP5 has a conserved motif in the catalytic domain that contains two binding sites for manganese (Mn²⁺ ) ions. Structural data indicate that two active site water molecules, one bridging the two Mn²⁺ ions and the other terminally coordinated with one of the Mn²⁺ ions (Mn1), are involved in catalysis. Recently, a density functional theory study revealed that the two water molecules can be both deprotonated to keep a neutral active site for catalysis. The theoretical study gives us an insight into the catalytic mechanism of PP5, but the knowledge of how the de

SUBMITTER: Wang L 

PROVIDER: S-EPMC5606534 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature