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A comparison of the dynamics of pantothenate synthetase from M. tuberculosis and E. coli : Computational studies
Author(s) -
Tan Yaw Sing,
Fuentes Gloria,
Verma Chandra
Publication year - 2011
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22994
Subject(s) - molecular dynamics , escherichia coli , dimer , chemistry , dynamics (music) , domain (mathematical analysis) , mycobacterium tuberculosis , biophysics , enzyme , physics , biochemistry , biology , computational chemistry , tuberculosis , gene , medicine , mathematical analysis , mathematics , organic chemistry , pathology , acoustics
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. Proteins 2011; © 2011 Wiley‐Liss, Inc.