Unliganded structure of human bisphosphoglycerate mutase reveals side-chain movements induced by ligand binding

A. Patterson, N. C. Price, J. Nairn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Erythrocyte-specific bisphosphoglycerate mutase is a trifunctional enzyme which modulates the levels of 2,3-bisphosphoglycerate (2,3-BPG) in red blood cells by virtue of its synthase and phosphatase activities. Low levels of erythrocyte 2,3-BPG increase the affinity of haemoglobin for oxygen, thus limiting the release of oxygen into tissues. 2,3-BPG levels in stored blood decline rapidly owing to the phosphatase activity of bisphosphoglycerate mutase, which is enhanced by a fall in pH. Here, the 1.94 A resolution X-ray structure of bisphosphoglycerate mutase is presented, focusing on the dynamic nature of key ligand-binding residues and their interaction with the inhibitor citrate. Residues at the binding pocket are complete. In addition, the movement of key residues in the presence and absence of ligand is described and alternative conformations are explored. The conformation in which the ligand citrate would bind at the substrate-binding pocket is proposed, with discussion and representations of its orientation. The characterization of bisphosphoglycerate mutase-citrate interactions will provide a framework for the design of specific inhibitors of the phosphatase activity of this enzyme, which may limit the decline of 2,3-BPG in stored blood.

Original languageEnglish
Pages (from-to)1415-1420
Number of pages6
JournalActa Crystallographica. Section F, Structural biology and crystallization communications
Volume66
DOIs
Publication statusPublished - Nov 2010

Keywords

  • bisphosphoglycerate mutase
  • citrate
  • enzyme inhibition
  • isothermal titration calorimetery
  • INDEPENDENT PHOSPHOGLYCERATE MUTASE
  • ENZYME-KINETIC EQUATIONS
  • CRYSTAL-STRUCTURE
  • 2,3-BISPHOSPHOGLYCERATE METABOLISM
  • CATALYTIC MECHANISM
  • RED-CELLS
  • MODEL
  • COMPLEX
  • FORM
  • INHIBITORS

Fingerprint

Dive into the research topics of 'Unliganded structure of human bisphosphoglycerate mutase reveals side-chain movements induced by ligand binding'. Together they form a unique fingerprint.

Cite this