Structural physiology of regulation mechanism of transport efficiency by P-glycoprotein

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670014
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Kyoto University
• Principal Investigator: Kato Hiroaki 京都大学, 薬学研究科(研究院), 教授 (90204487)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 構造生物学 / 受容体・膜輸送 / 薬理学 / X線結晶学

Outline of Final Research Achievements

We discovered that a repleacement of a Gln residue with Ala in a eukaryotic P-glycoprotein, euP-gp induced an increase of the basal ATP hydrolysis enzyme activity independent with a transport substrate, suggesting the Gln residue plays an important role in the coupling between ATP hydrolysis and active transport. To reveal this proposition, we determined the crystal structure of euP-gp and observed that the Gln residue connects an Ala residue in an alpha-helix of the other subunit by van der Waals force. This interaction may restrict the structural exchange between inward-open and outward-open states of the transporter, allowing to accumulate a torque that drives the reverse structural exchange of the transporter.

Free Research Field

構造生物学