http://hdl.handle.net/10027/7323 Thu, 23 May 2013 20:44:31 GMT 2013-05-23T20:44:31Z http://hdl.handle.net/10027/8544 Notes of a protein crystallographer: on the high-resolution structure of the PDB growth rate Abad-Zapatero, Cele © 2012 by Wiley-Blackwell, International Union of Crystallography, Acta Crystallographica Section D: Biological Crystallography. doi:10.1107/S0907444912004799 Tue, 01 May 2012 05:00:00 GMT http://hdl.handle.net/10027/8544 2012-05-01T05:00:00Z http://hdl.handle.net/10027/8324 Notes of a protein crystallographer: on the high-resolution structure of the PDB growth rate Abad-Zapatero, Cele This is a copy of an article published in Acta Crystallographica Section D: Biological Crystallography © 2012 International Union of Crystallography. Printed in Singapore – all rights reserved DOI: 10.1107/S0907444912004799 Tue, 01 May 2012 05:00:00 GMT http://hdl.handle.net/10027/8324 2012-05-01T05:00:00Z http://hdl.handle.net/10027/8302 The structure of ribosome-lankacidin complex reveals ribosomal sites for synergistic antibiotics Auerbach, Tamar; Mermershtain, Inbal; Davidovich, Chen; Bashan, Anat; Belousoff, Matthew; Wekselman, Itai; Zimmerman, Ella; Xiong, Liqun; Klepacki, Dorota; Mankin, Alexander; Yonath, Ada Crystallographic analysis revealed that the 17-member polyketide antibiotic lankacidin produced by Streptomyces rochei, binds at the peptidyl transferase center of the ubacterial large ribosomal subunit. Biochemical and functional studies verified this finding and showed interference with peptide bond formation. Chemical probing indicated that the macrolide lankamycin, an additional antibiotic produced by the same species, binds at a neighboring site, at the ribosome exit tunnel. Thus, it appears that lankacidin and lankamycin have been evolutionary optimized to interact with the ribosome simultaneously and that their dual action results in a synergistic inhibition of cell growth. The binding site of lankacidin and lankamycin partially overlap with the binding site of another pair of synergistic antibiotics, the streptogramins composing synercid. Thus, at least two pairs of structurally dissimilar compounds have been selected in the course of evolution to act synergistically by targeting neighboring sites in the ribosome. These results underscore the importance of the corresponding ribosomal sites for development of clinically-relevant synergistic antibiotics and demonstrate the utility of structural analysis for providing new directions for drug discovery. © 2010 by National Academy of Sciences. This is a copy of an article published in the Proceedings of the National Academy of Sciences © 2010. doi: 10.1073/pnas.0914100107 Fri, 01 Jan 2010 06:00:00 GMT http://hdl.handle.net/10027/8302 2010-01-01T06:00:00Z http://hdl.handle.net/10027/8192 Crystallization and preliminary X-ray characterization of the glpX-encoded class II fructose-1,6-bisphosphatase from Mycobacterium tuberculosis Gutka, Hiten J.; Franzblau, Scott G.; Movahedzadeh, Farahnaz; Abad-Zapatero, Cele Fructose-1,6-bisphosphatase (FBPase; EC 3.1.3.11), which is a key enzyme in gluconeogenesis, catalyzes the hydrolysis of fructose 1,6-bisphosphate to form fructose 6-phosphate and orthophosphate. The present investigation reports the crystallization and preliminary crystallographic studies of the glpX-encoded class II FBPase from Mycobacterium tuberculosis H37Rv. The recombinant protein, which was cloned using an Escherichia coli expression system, was purified and crystallized using the hanging-drop vapor-diffusion method. The crystals diffracted to a resolution of 2.7 Å and belonged to the hexagonal space group P6122, with unit-cell parameters a = b = 131.3, c = 143.2 Å. The structure has been solved by molecular replacement and is currently undergoing refinement. The original version is available through International Union of Crystallography at DOI: 10.1107/S1744309111014722. Wed, 01 Jun 2011 05:00:00 GMT http://hdl.handle.net/10027/8192 2011-06-01T05:00:00Z