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Inhibition of Mycobacterium tuberculosis Pantothenate Synthetase by Analogues of the Reaction Intermediate
Author(s) -
Ciulli Alessio,
Scott Duncan E.,
Ando Michiyo,
Reyes Fernando,
Saldanha S. Adrian,
Tuck Kellie L.,
Chirgadze Dimitri Y.,
Blundell Tom L.,
Abell Chris
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800437
Subject(s) - mycobacterium tuberculosis , adenylate kinase , enzyme , chemistry , small molecule , stereochemistry , dissociation (chemistry) , biochemistry , mycobacterium , computational biology , combinatorial chemistry , tuberculosis , biology , bacteria , genetics , medicine , organic chemistry , pathology
Get stuck in : Pantothenate synthetase is an attractive target for the development of novel small‐molecule drugs against Mycobacterium tuberculosis. Three related sulfamoyl adenylate inhibitors were designed to closely mimic the structure of the reaction intermediate, pantoyl adenylate. The most potent inhibitor exhibited dissociation and inhibition constants of about 100 n M . The structural elucidation of the compounds bound to the enzyme will aid development of subsequent inhibitors.