Conservation of functionally important global motions in an enzyme superfamily across varying quaternary structures.

The α-d-phosphohexomutase superfamily comprises enzymes involved in carbohydrate metabolism that are found in all kingdoms of life. Recent biophysical studies have shown for the first time that several of these enzymes exist as dimers in solution, prompting an examination of the oligomeric state of all proteins of known structure in the superfamily (11 different proteins; 31 crystal structures) via computational and experimental analyses. We find that these proteins range in quaternary structure from monomers to tetramers, with 6 of the 11 known structures being likely oligomers.

A coevolutionary residue network at the site of a functionally important conformational change in a phosphohexomutase enzyme family.

Coevolution analyses identify residues that co-vary with each other during evolution, revealing sequence relationships unobservable from traditional multiple sequence alignments. Here we describe a coevolutionary analysis of phosphomannomutase/phosphoglucomutase (PMM/PGM), a widespread and diverse enzyme family involved in carbohydrate biosynthesis. Mutual information and graph theory were utilized to identify a network of highly connected residues with high significance.

Solution NMR of a 463-residue phosphohexomutase: domain 4 mobility, substates, and phosphoryl transfer defect.

Phosphomannomutase/phosphoglucomutase contributes to the infectivity of Pseudomonas aeruginosa, retains and reorients its intermediate by 180°, and rotates domain 4 to close the deep catalytic cleft. Nuclear magnetic resonance (NMR) spectra of the backbone of wild-type and S108C-inactivated enzymes were assigned to at least 90%. (13)C secondary chemical shifts report excellent agreement of solution and crystallographic structure over the 14 α-helices, C-capping motifs, and 20 of the 22 β-strands.

Quaternary structure, conformational variability and global motions of phosphoglucosamine mutase.

Phosphoglucosamine mutase (PNGM) is a bacterial enzyme that participates in the peptidoglycan biosynthetic pathway. Recent crystal structures of PNGM from two bacterial pathogens, Bacillus anthracis and Francisella tularensis, have revealed key structural features of this enzyme for the first time. Here, we follow up on several novel findings from the crystallographic studies, including the observation of a structurally conserved interface between polypeptide chains and conformational variability of the C-terminal domain.

Crystal structure of Bacillus anthracis phosphoglucosamine mutase, an enzyme in the peptidoglycan biosynthetic pathway.

Phosphoglucosamine mutase (PNGM) is an evolutionarily conserved bacterial enzyme that participates in the cytoplasmic steps of peptidoglycan biosynthesis. As peptidoglycan is essential for bacterial survival and is absent in humans, enzymes in this pathway have been the focus of intensive inhibitor design efforts. Many aspects of the structural biology of the peptidoglycan pathway have been elucidated, with the exception of the PNGM structure.

Crystal structure of a bacterial phosphoglucomutase, an enzyme involved in the virulence of multiple human pathogens.

The crystal structure of the enzyme phosphoglucomutase from Salmonella typhimurium (StPGM) is reported at 1.7 A resolution. This is the first high-resolution structural characterization of a bacterial protein from this large enzyme family, which has a central role in metabolism and is also important to bacterial virulence and infectivity.