Crystal structures of Leishmania mexicana phosphoglycerate mutase suggest a one-metal mechanism and a new enzyme subclass

J Mol Biol. 2009 Dec 4;394(3):535-43. doi: 10.1016/j.jmb.2009.09.041. Epub 2009 Sep 23.


The structures of Leishmania mexicana cofactor-independent phosphoglycerate mutase (Lm iPGAM) crystallised with the substrate 3-phosphoglycerate at high and low cobalt concentrations have been solved at 2.00- and 1.90-A resolutions. Both structures are very similar and the active site contains both 3-phosphoglycerate and 2-phosphoglycerate at equal occupancies (50%). Lm iPGAM co-crystallised with the product 2-phosphoglycerate yields the same structure. Two Co(2+) are coordinated within the active site with different geometries and affinities. The cobalt at the M1 site has a distorted octahedral geometry and is present at 100% occupancy. The M2-site Co(2+) binds with distorted tetrahedral geometry, with only partial occupancy, and coordinates with Ser75, the residue involved in phosphotransfer. When the M2 site is occupied, the side chain of Ser75 adopts a position that is unfavourable for catalysis, indicating that this site may not be occupied under physiological conditions and that catalysis may occur via a one-metal mechanism. The geometry of the M2 site suggests that it is possible for Ser75 to be activated for phosphotransfer by H-bonding to nearby residues rather than by metal coordination. The 16 active-site residues of Lm iPGAM are conserved in the Mn-dependent iPGAM from Bacillus stearothermophilus (33% overall sequence identity). However, Lm iPGAM has an inserted tyrosine (Tyr210) that causes the M2 site to diminish in size, consistent with its reduced metal affinity. Tyr210 is present in trypanosomatid and plant iPGAMs, but not in the enzymes from other organisms, indicating that there are two subclasses of iPGAMs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain / genetics
  • Cobalt / metabolism
  • Conserved Sequence
  • Crystallography, X-Ray
  • Geobacillus stearothermophilus / enzymology
  • Geobacillus stearothermophilus / genetics
  • Hydrogen Bonding
  • Kinetics
  • Leishmania mexicana / enzymology*
  • Leishmania mexicana / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphoglycerate Mutase / chemistry*
  • Phosphoglycerate Mutase / classification
  • Phosphoglycerate Mutase / genetics
  • Phosphoglycerate Mutase / metabolism
  • Protein Conformation
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / classification
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Serine / chemistry
  • Species Specificity
  • Static Electricity


  • Protozoan Proteins
  • Recombinant Proteins
  • Cobalt
  • Serine
  • Phosphoglycerate Mutase

Associated data

  • PDB/3IGY
  • PDB/3IGZ