title: Crystal structure of a bioactive pactamycin analog bound to the 30S ribosomal subunit.
abstract: Biosynthetically and chemically derived analogs of the antibiotic pactamycin and de-6-methylsalicylyl (MSA)-pactamycin have attracted recent interest as potential antiprotozoal and antitumor drugs. Here, we report a 3.1-Å crystal structure of de-6-MSA-pactamycin bound to its target site on the Thermus thermophilus 30S ribosomal subunit. Although de-6-MSA-pactamycin lacks the MSA moiety, it shares the same binding site as pactamycin and induces a displacement of nucleic acid template bound at the E-site of the 30S. The structure highlights unique interactions between this pactamycin analog and the ribosome, which paves the way for therapeutic development of related compounds.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
authors.forename: David S
authors.initials: DS
authors.lastname: Tourigny
authors.forename: Israel S
authors.initials: IS
authors.lastname: Fernández
authors.forename: Ann C
authors.initials: AC
authors.lastname: Kelley
authors.forename: Ramkrishna Reddy
authors.initials: RR
authors.lastname: Vakiti
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Chattopadhyay
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dorich
authors.forename: Stephen
authors.initials: S
authors.lastname: Hanessian
authors.forename: V
authors.initials: V
authors.lastname: Ramakrishnan
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008968:Molecular Conformation; D010142:Pactamycin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000378:metabolism; D054680:Ribosome Subunits, Small, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D016963:Thermus thermophilus / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D012336:RNA, Ribosomal, 16S; D010142:Pactamycin
keywords: E-site; MSA; antibiotic; mRNA; methylsalicylyl; translation