Structural determinant for Helicobacter pylori resistance to sulfonamides

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Abstract

Bacterial dihydropterorate synthase (DHPS) is a key enzyme in the folic acid biosynthesis. In many pathogens, DHPS is the molecular target of sulfa drugs (sulfonamides). Sulfonamides act as competitive inhibitors by occupying the binding pocket for the substrate p-aminobenzoic acid. Despite the high degree of crossspecies sequence conservation in the p-aminobenzoic-acid-binding site, some bacteria are not sensitive to these drugs. This work addresses the molecular mechanism of resistance of Helicobacter pylori DHPS to sulfonamides. Homology modelling, structural and sequence analysis identify a single amino acid substitution in the substrate-binding pocket as the major determinant for its resistance. Structure-guided rational modification of sulfonamides to fit the specific architecture of the H. pylori enzyme s active site may be a strategy to develop novel antimicrobial agents with specific activity against H. pylori.
Original languageEnglish
Title of host publicationRecent Advances in Biomedical & Chemical Engineering and Materials Science
EditorsManijeh Razeghi, Jun Zhang, Samuel Lofland, Emanuel E Strehler, George Perry, John Gordon Lindsay, Photios A Anninos
Place of PublicationUSA
PublisherRecent Advances in Biomedical & Chemical Engineering and Materials Science
Pages76 - 78
Number of pages3
ISBN (Print)9781618042231
Publication statusPublished - 2014
EventInternational Conference on Biology and Biomedical Engineering (BBE 2014) - Venice, Italy
Duration: 15 Mar 201417 Mar 2014
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Conference

ConferenceInternational Conference on Biology and Biomedical Engineering (BBE 2014)
Abbreviated titleBBE 2014
CountryItaly
CityVenice
Period15/03/1417/03/14
OtherRECENT ADVANCES in BIOMEDICAL & CHEMICAL ENGINEERING and MATERIALS SCIENCE Proceedings of the 2014 International Conference on Chemical Engineering and Materials Science (CEMS '14) Proceedings of the 2014 International Conference on Biology and Biomedical Engineering (BBE '14) Venice, Italy March 15‐17, 2014
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