Open AccessThe Mechanism of the Inhibition of Gramicidin‐S Synthesis by d ‐Leucine
Author(s) -
Saxholm Harald,
Zimmer TrineLise,
Laland Søen G.
Publication year - 1972
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1972.tb02080.x
Subject(s) - leucine , chemistry , stereochemistry , tetrapeptide , pentapeptide repeat , thioester , gramicidin s , enzyme , biochemistry , peptide , gramicidin , amino acid , membrane
The results show that enzyme I of gramicidin S synthetase activates d ‐leucine in a manner analogous to that of l ‐leucine (ATP + d ‐leucine ⇌ d ‐leucyl‐adenylate + PP 1 ) and binds two moles of d ‐leucine in thioester linkage. It has therefore two thiol sites for d ‐leucine, compared to one for the l ‐isomer. One of the sites seems to be the thiol site for L ‐leucine which is therefore stereo‐unspecific. The results also indicate that the site for the formation of the aminoacyl adenylates is the same for the two isomers. In contrast to thioester‐bound l ‐leucine, enzyme‐bound D ‐leucine does not catalyze the ATP‐[ 14 C]AMP exchange reaction. At a molar ratio of l ‐leucine: D ‐leucine equal to 4, gramicidin S synthesis is almost completely inhibited and the growth of the peptide chain stops at the tetrapeptide stage ( D ‐Phe‐ l ‐Pro‐ l ‐Val‐ L ‐Orn). Enzyme‐bound D ‐leucine is thus not able to replace L ‐leucine in the formation of the pentapeptide.