Structural highlights
Publication Abstract from PubMedTyrocidine, a macrocyclic decapeptide from Bacillus brevis, is nonribosomally assembled by a set of multimodular peptide synthetases, which condense two D-amino acids and eight L-amino acids to produce this membrane-disturbing antibiotic. D-Phenylalanine, the first amino acid incorporated into tyrocidine, is catalytically derived from enzyme-bound L-Phe by the C-terminal epimerization (E) domain of tyrocidine synthetase A (TycA). The 1.5 A resolution structure of the cofactor-independent TycA E domain reveals an intimate relationship to the condensation (C) domains of peptide synthetases. In contrast to the latter, the TycA E domain uses an enlarged bridge region to plug the active-site canyon from the acceptor side, whereas at the donor side a latch-like floor loop is suitably extended to accommodate the alphaIII helix of the preceding peptide-carrier domain. Additionally, E domains exclusively harbour a conserved glutamate residue, Glu882, that is opposite the active-site residue His743. This active-site topology implies Glu882 as a candidate acid-base catalyst, whereas His743 stabilizes in the protonated state a transient enolate intermediate of the L<-->D isomerization. Structure of the epimerization domain of tyrocidine synthetase A.,Samel SA, Czodrowski P, Essen LO Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1442-52. doi:, 10.1107/S1399004714004398. Epub 2014 Apr 30. PMID:24816112[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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