title: A comparison of the dynamics of pantothenate synthetase from M. tuberculosis and E. coli: computational studies.
abstract: Pantothenate synthetase (PS) catalyzes the final step of the pantothenate pathway, in which pantothenate is formed from pantoate and β-alanine in an ATP-dependent reaction. Mycobacterium tuberculosis PS (MTB PS) is functionally a dimer and a potential target for novel antitubercular drugs. Molecular dynamics simulations show that the functional dynamics of the enzyme are dominated by motions of a flexible gate loop in the N-terminal domain and of the C-terminal domain. The gate loop motions dominate in MTB PS while the C-terminal domain motion dominates in Escherichia coli PS. Simulations also show that the correlated motions of the domains are severely compromised in the monomeric forms. Mutations that reduce the mobility of the gate loop in MTB PS and increased it in E. coli PS were designed and validated through simulations.
authors.affiliation: Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore 138671.
authors.forename: Yaw Sing
authors.initials: YS
authors.lastname: Tan
authors.forename: Gloria
authors.initials: G
authors.lastname: Fuentes
authors.forename: Chandra
authors.initials: C
authors.lastname: Verma
mesh_terms: D000595:Amino Acid Sequence; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology*; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000201:enzymology*; D010453:Peptide Synthases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D010453:Peptide Synthases; C022318:pantothenate synthetase