A β-sheet structure formed by C–H…O hydrogen bonds between the thiazole rings and amide bonds of a dimeric desoxazoline ascidiacyclamide analogue

Akiko Asano, Taizo Taniguchi, Masahiro Sasaki, Hiroshi Hasegawa, Yoshio Katsuya and Mitsunobu Doi, Acta Cryst. (2001). E57, o834–o838

This interesting and valuable paper illustrates how much novel information can be derived from one crystal structure and compressed into a small package. The investigators have introduced a non-standard amino acid into a cyclic antibiotic in order to probe the structural determinants of protein folding. In the process, they have elucidated the conformational flexibility of the unusual peptide as well as the cyclic structure, and demonstrated an important role for CH…O hydrogen bonding in the structure. Although the amino acid introduced in the cyclic peptide has not been detected in ribosomally encoded proteins, the recent identification of the occurrence of pyrrolysine in ribosomally encoded peptides in the Archaea Methanosarcina barkeri [Science, 296, 1459 (2002)] and its consequent characterization as the '22nd Amino Acid', raises the possibility that in some species (of the 500,000 or more for which the genetic code has not been unequivocally determined) unusual amino acids such as this may actually be ribosomally encoded in proteins. The CH…O hydrogen bond remains controversial despite numerous observations. This structure presents a very good example of a strong CH…O hydrogen bond involved in defining conformation. Recent observations of such hydrogen bonds in protein structures include cases of stabilization of protein fold, and participation in cofactor binding and protein function.

Reviewed by William L. Duax
Hauptman-Woodward Medical Research Inst., USA