Structural and mechanistic insights into KslB, a bacterial Pictet-Spenglerase in kitasetaline biosynthesis.

ABSTRACT: KslB is one of the few bacterial Pictet-Spenglerases recently identified in the biosynthesis of the β-carboline compound kitasetaline. While previous in vitro studies established that KslB catalyzes the condensation between l-tryptophan and α-ketoglutarate, the reaction mechanism, particularly its stereochemistry, remains poorly understood. This study presents five crystal structures of KslB, capturing key stages of reaction, shedding light on its catalytic dynamics. Among these, alternative binding poses of substrate and reaction product highlighted two significant features: (1) an additional pocket that accommodates l-tryptophan, and (2) two positively charged residues, Lys264 and Arg256, which form salt bridges with the product C1' and C5' carboxylate groups derived from α-ketogl

SUBMITTER: Kim W 

PROVIDER: S-EPMC12012969 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature