Crystal Structure of a Bioactive Pactamycin Analog Bound to the 30S Ribosomal Subunit

被引:17
作者
Tourigny, David S. [1 ]
Fernandez, Israel S. [1 ]
Kelley, Ann C. [1 ]
Vakiti, Ramkrishna Reddy [2 ]
Chattopadhyay, Amit Kumar [2 ]
Dorich, Stephane [2 ]
Hanessian, Stephen [2 ]
Ramakrishnan, V. [1 ]
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 0QH, England
[2] Univ Montreal, Dept Chem, Stn Ctr Vile, Montreal, PQ H3C 3J7, Canada
基金
英国医学研究理事会; 英国惠康基金; 加拿大自然科学与工程研究理事会;
关键词
ANTIBIOTICS; ANTITUMOR; RNA; BINDING; SITES;
D O I
10.1016/j.jmb.2013.05.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Biosynthetically and chemically derived analogs of the antibiotic pactamycin and de-6-methylsalicyly1 (MSA)-pactarnycin have attracted recent interest as potential antiprotozoal and antitumor drugs. Here, we report a 3.1-angstrom 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. (C) 2013 The Authors. Published by Elsevier Ltd. All tights reserved.
引用
收藏
页码:3907 / 3910
页数:4
相关论文
共 16 条
  • [1] Bhuyan B. K., 1961, ANTIMICROB AGENTS CH, V184, P1050
  • [2] The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit
    Brodersen, DE
    Clemons, WM
    Carter, AP
    Morgan-Warren, RJ
    Wimberly, BT
    Ramakrishnan, V
    [J]. CELL, 2000, 103 (07) : 1143 - 1154
  • [3] Pactamycin Made Easy
    Codelli, Julian A.
    Reisman, Sarah E.
    [J]. SCIENCE, 2013, 340 (6129) : 152 - 153
  • [4] Dissecting the ribosomal inhibition mechanisms of edeine and pactamycin: The universally conserved residues G693 and C795 regulate P-site RNA binding
    Dinos, G
    Wilson, DN
    Teraoka, Y
    Szaflarski, W
    Fucini, P
    Kalpaxis, D
    Nierhaus, KH
    [J]. MOLECULAR CELL, 2004, 13 (01) : 113 - 124
  • [5] SYNTHESIS OF SPARSOMYCIN ANALOGS AS POTENTIAL ANTITUMOR AGENTS
    DUBOIS, RJ
    LIN, CCL
    MICHEL, BL
    [J]. JOURNAL OF PHARMACEUTICAL SCIENCES, 1975, 64 (05) : 825 - 829
  • [6] BINDING-SITES OF THE ANTIBIOTICS PACTAMYCIN AND CELESTICETIN ON RIBOSOMAL-RNAS
    EGEBJERG, J
    GARRETT, RA
    [J]. BIOCHIMIE, 1991, 73 (7-8) : 1145 - 1149
  • [7] Total Synthesis of Pactamycin
    Hanessian, Stephen
    Vakiti, Ramkrishna Reddy
    Dorich, Stephane
    Banerjee, Shyamapada
    Lecomte, Fabien
    DelValle, Juan R.
    Zhang, Jianbin
    Deschenes-Simard, Benoit
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2011, 50 (15) : 3497 - 3500
  • [8] Probing functional diversity in pactamycin toward antibiotic, antitumor, and antiprotozoal activity
    Hanessian, Stephen
    Vakiti, Ramkrishna Reddy
    Chattopadhyay, Amit Kumar
    Dorich, Stephane
    Lavallee, Christian
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (07) : 1775 - 1786
  • [9] Deciphering Pactamycin Biosynthesis and Engineered Production of New Pactamycin Analogues
    Ito, Takuya
    Roongsawang, Niran
    Shirasaka, Norifumi
    Lu, Wanli
    Flatt, Patricia M.
    Kasanah, Noer
    Miranda, Cristobal
    Mahmud, Taifo
    [J]. CHEMBIOCHEM, 2009, 10 (13) : 2253 - 2265
  • [10] Biosynthetic Studies and Genetic Engineering of Pactamycin Analogs with Improved Selectivity toward Malarial Parasites
    Lu, Wanli
    Roongsawang, Niran
    Mahmud, Taifo
    [J]. CHEMISTRY & BIOLOGY, 2011, 18 (04): : 425 - 431