Enzyme structure with two catalytic sites for double-sieve selection of substrate

被引:313
作者
Nureki, O
Vassylyev, DG
Tateno, M
Shimada, A
Nakama, T
Fukai, S
Konno, M
Hendrickson, TL
Schimmel, P
Yokoyama, S
机构
[1] Univ Tokyo, Grad Sch Sci, Dept Biochem & Biophys, Bunkyo Ku, Tokyo 113, Japan
[2] RIKEN, Inst Phys & Chem Res, Wako, Saitama 35101, Japan
[3] Matsushita Elect Ind Co Ltd, Int Inst Adv Res, Cent Res Labs, Kyoto 61902, Japan
[4] Ochanomizu Univ, Fac Sci, Dept Chem, Bunkyo Ku, Tokyo 112, Japan
[5] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
关键词
D O I
10.1126/science.280.5363.578
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
High-fidelity transfers of genetic information in the central dogma can be achieved by a reaction called editing. The crystal structure of an enzyme with editing activity in translation is presented here at 2.5 angstroms resolution. The enzyme, isoleucyl-transfer RNA synthetase, activates not only the cognate substrate L-isoleucine but also the minimally distinct L-valine in the first, aminoacylation step. Then, in a second, "editing" step, the synthetase itself rapidly hydrolyzes only the valylated products. For this two-step substrate selection, a "double-sieve" mechanism has already been proposed. The present crystal structures of the synthetase in complexes with L-isoleucine and L-valine demonstrate that the first sieve is on the aminoacylation domain containing the Rossmann fold, whereas the second, editing sieve exists on a globular beta-barrel domain that protrudes from the aminoacylation domain.
引用
收藏
页码:578 / 582
页数:5
相关论文
共 34 条
  • [31] EVIDENCE FOR DISPENSABLE SEQUENCES INSERTED INTO A NUCLEOTIDE FOLD
    STARZYK, RM
    WEBSTER, TA
    SCHIMMEL, P
    [J]. SCIENCE, 1987, 237 (4822) : 1614 - 1618
  • [32] MOLECULAR-STRUCTURE OF THE ACYL-ENZYME INTERMEDIATE IN BETA-LACTAM HYDROLYSIS AT 1.7 ANGSTROM RESOLUTION
    STRYNADKA, NCJ
    ADACHI, H
    JENSEN, SE
    JOHNS, K
    SIELECKI, A
    BETZEL, C
    SUTOH, K
    JAMES, MNG
    [J]. NATURE, 1992, 359 (6397) : 700 - 705
  • [33] CONTRIBUTION OF HYDROPHOBIC RESIDUES TO THE STABILITY OF HUMAN LYSOZYME - CALORIMETRIC STUDIES AND X-RAY STRUCTURAL-ANALYSIS OF THE 5-ISOLEUCINE TO VALINE MUTANTS
    TAKANO, K
    OGASAHARA, K
    KANEDA, H
    YAMAGATA, Y
    FUJII, S
    KANAYA, E
    KIKUCHI, M
    OOBATAKE, M
    YUTANI, K
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1995, 254 (01) : 62 - 76
  • [34] Zhang ZY, 1996, CANCER RES, V56, P3926