Analysis of Burkholderia pseudomallei IspF in complex with sulfapyridine, sulfamonomethoxine, ethoxzolamide and acetazolamide
Dakota Grote
Northern Illinois University, Department of Chemistry and Biochemistry, 1425 Lincoln Highway, DeKalb, IL, 60115 USA
Search for more papers by this authorChristopher G. Stewart
Northern Illinois University, Department of Chemistry and Biochemistry, 1425 Lincoln Highway, DeKalb, IL, 60115 USA
Search for more papers by this authorDrashti G. Daraji
Northern Illinois University, Department of Chemistry and Biochemistry, 1425 Lincoln Highway, DeKalb, IL, 60115 USA
Search for more papers by this authorParisa Enayati
Northern Illinois University, Department of Chemistry and Biochemistry, 1425 Lincoln Highway, DeKalb, IL, 60115 USA
Search for more papers by this authorKristina N. Braverman
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
Search for more papers by this authorCeAnn Romanaggi
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
Search for more papers by this authorMadison J. Bolejack
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorJason K. Yano
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
Search for more papers by this authorJan Abendroth
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorDavid M. Dranow
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorPhillip G. Pierce
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorDonald D. Lorimer
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorPeter S. Horanyi
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorBart L. Staker
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
Seattle Children's Research Institute, Center for Global Infectious Disease Research, 307 Westlake Avenue North, Seattle, WA, 98109 USA
Search for more papers by this authorThomas E. Edwards
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorCorresponding Author
Peter J. Myler
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
Seattle Children's Research Institute, Center for Global Infectious Disease Research, 307 Westlake Avenue North, Seattle, WA, 98109 USA
University of Washington, Departments of Pediatrics, Biomedical Informatics and Medical Education, and Global Health, Seattle, WA, 98195 USA
Peter J. Myler, e-mail: [email protected]; James R. Horn, e-mail: [email protected]; Timothy J. Hagen, e-mail: [email protected]Search for more papers by this authorCorresponding Author
James R. Horn
Northern Illinois University, Department of Chemistry and Biochemistry, 1425 Lincoln Highway, DeKalb, IL, 60115 USA
Peter J. Myler, e-mail: [email protected]; James R. Horn, e-mail: [email protected]; Timothy J. Hagen, e-mail: [email protected]Search for more papers by this authorCorresponding Author
Timothy J. Hagen
Northern Illinois University, Department of Chemistry and Biochemistry, 1425 Lincoln Highway, DeKalb, IL, 60115 USA
Peter J. Myler, e-mail: [email protected]; James R. Horn, e-mail: [email protected]; Timothy J. Hagen, e-mail: [email protected]Search for more papers by this authorDakota Grote
Northern Illinois University, Department of Chemistry and Biochemistry, 1425 Lincoln Highway, DeKalb, IL, 60115 USA
Search for more papers by this authorChristopher G. Stewart
Northern Illinois University, Department of Chemistry and Biochemistry, 1425 Lincoln Highway, DeKalb, IL, 60115 USA
Search for more papers by this authorDrashti G. Daraji
Northern Illinois University, Department of Chemistry and Biochemistry, 1425 Lincoln Highway, DeKalb, IL, 60115 USA
Search for more papers by this authorParisa Enayati
Northern Illinois University, Department of Chemistry and Biochemistry, 1425 Lincoln Highway, DeKalb, IL, 60115 USA
Search for more papers by this authorKristina N. Braverman
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
Search for more papers by this authorCeAnn Romanaggi
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
Search for more papers by this authorMadison J. Bolejack
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorJason K. Yano
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
Search for more papers by this authorJan Abendroth
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorDavid M. Dranow
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorPhillip G. Pierce
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorDonald D. Lorimer
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorPeter S. Horanyi
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorBart L. Staker
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
Seattle Children's Research Institute, Center for Global Infectious Disease Research, 307 Westlake Avenue North, Seattle, WA, 98109 USA
Search for more papers by this authorThomas E. Edwards
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
UCB Biosciences, Bainbridge Island, WA, 98110 USA
Search for more papers by this authorCorresponding Author
Peter J. Myler
Seattle Structural Genomics Center for Infectious Disease (SSGCID), Seattle, WA, 98109 USA
Seattle Children's Research Institute, Center for Global Infectious Disease Research, 307 Westlake Avenue North, Seattle, WA, 98109 USA
University of Washington, Departments of Pediatrics, Biomedical Informatics and Medical Education, and Global Health, Seattle, WA, 98195 USA
Peter J. Myler, e-mail: [email protected]; James R. Horn, e-mail: [email protected]; Timothy J. Hagen, e-mail: [email protected]Search for more papers by this authorCorresponding Author
James R. Horn
Northern Illinois University, Department of Chemistry and Biochemistry, 1425 Lincoln Highway, DeKalb, IL, 60115 USA
Peter J. Myler, e-mail: [email protected]; James R. Horn, e-mail: [email protected]; Timothy J. Hagen, e-mail: [email protected]Search for more papers by this authorCorresponding Author
Timothy J. Hagen
Northern Illinois University, Department of Chemistry and Biochemistry, 1425 Lincoln Highway, DeKalb, IL, 60115 USA
Peter J. Myler, e-mail: [email protected]; James R. Horn, e-mail: [email protected]; Timothy J. Hagen, e-mail: [email protected]Search for more papers by this authorAbstract
The methylerythritol phosphate (MEP) pathway is a metabolic pathway that produces the isoprenoids isopentyl pyrophosphate and dimethylallyl pyrophosphate. Notably, the MEP pathway is present in bacteria and not in mammals, which makes the enzymes of the MEP pathway attractive targets for the discovery of new anti-infective agents due to the reduced chances of off-target interactions leading to side effects. There are seven enzymes in the MEP pathway, the fifth of which is IspF. Crystal structures of Burkholderia pseudomallei IspF were determined with five different sulfonamide ligands bound. The sulfonamide-containing ligands were ethoxzolamide, acetazolamide, sulfapyridine and sulfamonomethoxine. The fifth bound ligand was a synthetic analog of acetazolamide. All ligands coordinated to the active-site Zn+2 ion through the sulfonamide group, although sulfapyridine and sulfamonomethoxine, both of which are known antibacterial agents, possess similar binding interactions that are distinct from the other three sulfonamides. These structural data will aid in the discovery of new IspF inhibitors.
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