Three ring posttranslational circuses: insertion of oxazoles, thiazoles, and pyridines into protein-derived frameworks.
Nitrogen heterocycles are the key functional and structural elements in both RNA and DNA, in half a dozen of the most important coenzymes, and in many synthetic drug scaffolds. On the other hand, only 3 of 20 proteinogenic amino acids have nitrogen heterocycles: proline, histidine, and tryptophan. This inventory can be augmented in microbial proteins by posttranslational modifications downstream of leader peptide regions that convert up to 10 serine, threonine, and cysteine residues, side chains and peptide backbones, into oxazoles, thiazoles, and pyridine rings. Subsequent proteolysis releases these heterocyclic scaffolds in both linear and macrocyclic frameworks as bioactive small molecules.
Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, United States. christopher_walsh@hms.harvard.edu
Christopher T
CT
Walsh
Steven J
SJ
Malcolmson
Travis S
TS
Young
D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D010080:Oxazoles / Q000737:chemistry / Q000378:metabolism*; D011392:Proline / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism*; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism*; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism
D010080:Oxazoles; D011506:Proteins; D011725:Pyridines; D013844:Thiazoles; D006639:Histidine; D014364:Tryptophan; D011392:Proline