STRUCTURE OF BALHIMYCIN AND ITS COMPLEX WITH SOLVENT MOLECULES

Balhimycin is a naturally occurring glycopeptide antibiotic, related t o vancomycin which acts by binding nascent bacterial cell-wall peptide ending in the sequence D-Ala-D-Ala. Crystals of balhimycin are monocl inic, space group P2(1), a = 20.48(10), b = 43.93 (21), c = 27.76(14) Angstrom, beta = 100.5(5)degrees with four independent antibiotic mole cules, three molecules of 2-methyl-2,4-pentanediol, two citrate ions, three acetate ions and 127.5 water molecules in the asymmetric unit. W ith an asymmetric unit larger than those of the smallest proteins and a solvent content of about 32%, the crystals have similar diffraction properties to those of small proteins. 27 387 unique reflections were collected using synchrotron radiation. The structure was solved by a s tandard protein technique, the molecular-replacement method, using ure ido-balhimycin as search model. The anisotropic refinement against all F-2 data between 0.96 and 45 Angstrom converged to a conventional R v alue of 11.27% with R1 = Sigma \\F-o\ - \F-c\\/Sigma\F-o\ for the 24 6 23 data with I > 2 sigma(I) and 12.58% for all 27 387 data. The four m onomers possess fairly similar conformations (r.m.s. deviation 0.7 Ang strom). Two antibiotic molecules form a tight dimer with antiparallel hydrogen bonds between the peptide backbone as well as between the van cosamine residues and the peptide backbone. In each of the two dimers, one binding pocket is occupied by a citrate ion and the other by an a cetate ion. The dimer units are linked in the crystal by hydrogen bond s to form infinite chains.