Molecular recognition of tyrosinyl adenylate analogues by prokaryotic tyrosyl tRNA synthetases

被引：52

作者：

Brown, P ^{[1
]}

Richardson, CM ^{[1
]}

Mensah, LM ^{[1
]}

O'Hanlon, PJ ^{[1
]}

Osborne, NF ^{[1
]}

Pope, AJ ^{[1
]}

Walker, G ^{[1
]}

机构：

[1] SmithKline Beecham Pharmaceut, Harlow CM19 5AW, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1999年 / 7卷 / 11期

关键词：

amino acids and derivatives; enzyme inhibitors; molecular modelling; X-ray crystal structures; homology modelling;

D O I：

10.1016/S0968-0896(99)00192-3

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：

Molecular modelling and synthetic studies have been carried out on tyrosinyl adenylate and analogues to probe the interactions seen in the active site of the X-ray crystal structure of tyrosyl tRNA synthetase from Bacillus stearothermophilus, and to search for new inhibitors of this enzyme, Micromolar and sub-micromolar inhibitors of tyrosyl tRNA synthetases from both B. stearothermophilus and Staphylococcus aureus have been synthesised. The importance of the adenine ring to the binding of tyrosinyl adenylate to the enzyme, and the importance of water-mediated hydrogen bonding interactions, have been highlighted. The inhibition data has been further supported by homology modelling with the S. aureus enzyme, and by ligand docking studies. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：2473 / 2485

页数：13

共 25 条

[1] CAMBRIDGE CRYSTALLOGRAPHIC DATA CENTER - COMPUTER-BASED SEARCH, RETRIEVAL, ANALYSIS AND DISPLAY OF INFORMATION [J].

ALLEN, FH ;

BELLARD, S ;

BRICE, MD ;

CARTWRIGHT, BA ;

DOUBLEDAY, A ;

HIGGS, H ;

HUMMELINK, T ;

HUMMELINKPETERS, BG ;

KENNARD, O ;

MOTHERWELL, WDS ;

RODGERS, JR ;

WATSON, DG .

ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE, 1979, 35 (OCT) :2331-2339

[2]

ARNEZ JG, 1997, TRENDS BIOCHEM SCI, V22, P189

[3] C-NUCLEOSIDE STUDIES .16. THE ISOPROPYLIDENATION OF D-RIBOSE DIETHYL DITHIOACETAL AND RIBITOL - A NEW SYNTHESIS OF ALPHA-D-RIBOFURANUSYLETHYNE AND BETA-D-RIBOFURANOSYLETHYNE VIA 2,3-4,5-DI-O-ISOPROPYLIDENE-ALDEHYDO-D-RIBOSE [J].

ASLANISHOTORBANI, G ;

BUCHANAN, JG ;

EDGAR, AR ;

SHAHIDI, PK .

CARBOHYDRATE RESEARCH, 1985, 136 (FEB) :37-52

[4]

BELRHALI H, 1994, SCIENCE, V263, P1423

[5] STRUCTURE OF TYROSYL TRANSFER-RNA SYNTHETASE REFINED AT 2.3-A RESOLUTION - INTERACTION OF THE ENZYME WITH THE TYROSYL ADENYLATE INTERMEDIATE [J].

BRICK, P ;

BHAT, TN ;

BLOW, DM .

JOURNAL OF MOLECULAR BIOLOGY, 1989, 208 (01) :83-98

[6]

CALENDER R, 1966, BIOCHEMISTRY-US, V5, P168

[7] SELECTIVE INHIBITION OF AMINOACYL RIBONUCLEIC ACID SYNTHETASES BY AMINOALKYL ADENYLATES [J].

CASSIO, D ;

LEMOINE, F ;

WALLER, JP ;

SANDRIN, E ;

BOISSONN.RA .

BIOCHEMISTRY, 1967, 6 (03) :827-&

[8] A FACILE SYNTHESIS OF ASCAMYCIN AND RELATED ANALOGS [J].

CASTROPICHEL, J ;

GARCIALOPEZ, MT ;

DELASHERAS, FG .

TETRAHEDRON, 1987, 43 (02) :383-389

[9]

CHLADEK S, 1964, COLLECT CZECH CHEM C, V29, P214

[10] Glutamyl adenylate analogues are inhibitors of glutamyl-tRNA synthetase [J].

Desjardins, M ;

Garneau, S ;

Desgagnés, J ;

Lacoste, L ;

Yang, F ;

Lapointe, J ;

Chênevert, R .

BIOORGANIC CHEMISTRY, 1998, 26 (01) :1-13

← 1 2 3 →