3. What product is formed when sulphanilamide binds to the enzyme dihydropteroate synthase rather than the...

3. What product is formed when sulphanilamide binds to the enzyme dihydropteroate synthase rather than the natural substrate PABA? How does this result in the inhibition of bacterial growth?

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Hi Answer:

Answer: Dihydropteroate synthase (DHPS) is the enzyme which produces dihydropteroate in bacteria. DHPS is mainly participating in the folate synthesis pathway. There are two binding pockets are recognized in this enzyme, one is for dihydropterin pyrophosphate (DHPP) and second is for p-amino benzoic acid (pABA) binding. The enzyme DHPS catalyzed the reaction with these two substrates and produce dihydropteroic acid (C₁₄H₁₄N₆O₃) which is one of the important intermediates of folate synthesis pathway. We know that the folate synthesis pathway is essential pathway for the amino acid synthesis and if the amino acid synthesis is inhibited then in the absence of the amino acids, bacteria can not survive.

When we target the pABA pocket of DHPS enzyme by replacing it with sulfonamide which is substrate analogues and compete with the para-aminobenzoic acid (pABA), then there is no formation of dihydropteroic acid (C₁₄H₁₄N₆O₃) which inhibits the folate synthesis pathway and ultimately kill the bacteria, but it is observed that due to the high clinical usage of sulfonamides, several bacterial species developed resistance to this method and they are not killed by replacing the pABA with sulfonamide. The diagrammatic view of whole (normal & altered) pathway is given below.

gladiator answered 2 years ago

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