High Resolution Structure of the Phosphohistidine-activated Form of Escherichia coli Cofactor-dependent Phosphoglycerate Mutase

• Published in: The Journal of biological chemistry Vol. 276; no. 5; pp. 3247 - 3253
• Main Authors: Bond, Charles S., White, Malcolm F., Hunter, William N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.02.2001; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Binding Sites; Escherichia coli; Escherichia coli - enzymology; Histidine - metabolism; Models, Molecular; Molecular Sequence Data; Phosphoglycerate Mutase - chemistry; Phosphoglycerate Mutase - metabolism; phosphohistidine; Phosphorylation; Protein Folding; Protein Structure, Quaternary; Sequence Homology, Amino Acid
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M007318200

The active conformation of the dimeric cofactor-dependent phosphoglycerate mutase (dPGM) fromEscherichia coli has been elucidated by crystallographic methods to a resolution of 1.25 Å (R-factor 0.121;R-free 0.168). The active site residue His10, central in the catalytic mechanism of dPGM, is present as a phosphohistidine with occupancy of 0.28. The structural changes on histidine phosphorylation highlight various features that are significant in the catalytic mechanism. The C-terminal 10-residue tail, which is not observed in previous dPGM structures, is well ordered and interacts with residues implicated in substrate binding; the displacement of a loop adjacent to the active histidine brings previously overlooked residues into positions where they may directly influence catalysis. E. coli dPGM, like the mammalian dPGMs, is a dimer, whereas previous structural work has concentrated on monomeric and tetrameric yeast forms. We can now analyze the sequence differences that cause this variation of quaternary structure.