CRYSTAL-STRUCTURE OF RECOMBINANT HUMAN T-CELL CYCLOPHILIN-A AT 2.5-A RESOLUTION

被引:192
作者
KE, HM [1 ]
ZYDOWSKY, LD [1 ]
LIU, J [1 ]
WALSH, CT [1 ]
机构
[1] HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115
关键词
X-RAY CRYSTALLOGRAPHY; IMMUNOSUPPRESSIVE DRUG BINDING PROTEIN; PEPTIDYL-PROLYL ISOMERASE; CYCLOSPORINE-A;
D O I
10.1073/pnas.88.21.9483
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
The structure of the unligated human T-cell recombinant cyclophilin has been determined at 3 angstrom resolution by multiple isomorphous replacement methods and refined at 2.5 angstrom resolution to an R factor of 0.209. The root-mean-square errors of the bond lengths and bond angles are 0.013 angstrom and 2.8-degrees from ideal geometry, respectively. The overall structure is a beta-barrel, consisting of eight antiparallel beta-strands wrapping around the barrel surface and two alpha-helices sitting on the top and the bottom closing the barrel. Inside the barrel, seven aromatic and other hydrophobic residues form a compact hydrophobic core. A loop of Lys-118 to His-126 and four beta-strands (B3-B6) constitute a pocket we speculate to be the binding site of cyclosporin A.
引用
收藏
页码:9483 / 9487
页数:5
相关论文
共 38 条
[1]   CRYSTALLOGRAPHIC R-FACTOR REFINEMENT BY MOLECULAR-DYNAMICS [J].
BRUNGER, AT ;
KURIYAN, J ;
KARPLUS, M .
SCIENCE, 1987, 235 (4787) :458-460
[2]   ORTHOGONAL PACKING OF BETA-PLEATED SHEETS IN PROTEINS [J].
CHOTHIA, C ;
JANIN, J .
BIOCHEMISTRY, 1982, 21 (17) :3955-3965
[3]   H-1-NMR STUDIES ON BOVINE CYCLOPHILIN - PRELIMINARY STRUCTURAL CHARACTERIZATION OF THIS SPECIFIC CYCLOSPORINE-A BINDING-PROTEIN [J].
DALGARNO, DC ;
HARDING, MW ;
LAZARIDES, A ;
HANDSCHUMACHER, RE ;
ARMITAGE, IM .
BIOCHEMISTRY, 1986, 25 (22) :6778-6784
[4]   NMR-STUDIES OF [U-C-13]CYCLOSPORIN-A BOUND TO CYCLOPHILIN - BOUND CONFORMATION AND PORTIONS OF CYCLOSPORINE INVOLVED IN BINDING [J].
FESIK, SW ;
GAMPE, RT ;
EATON, HL ;
GEMMECKER, G ;
OLEJNICZAK, ET ;
NERI, P ;
HOLZMAN, TF ;
EGAN, DA ;
EDALJI, R ;
SIMMER, R ;
HELFRICH, R ;
HOCHLOWSKI, J ;
JACKSON, M .
BIOCHEMISTRY, 1991, 30 (26) :6574-6583
[5]   ISOTOPE-EDITED NMR OF CYCLOSPORINE-A BOUND TO CYCLOPHILIN - EVIDENCE FOR A TRANS-9,10 AMIDE BOND [J].
FESIK, SW ;
GAMPE, RT ;
HOLZMAN, TF ;
EGAN, DA ;
EDALJI, R ;
LULY, JR ;
SIMMER, R ;
HELFRICH, R ;
KISHORE, V ;
RICH, DH .
SCIENCE, 1990, 250 (4986) :1406-1409
[6]   CYCLOPHILIN AND PEPTIDYL-PROLYL CIS-TRANS ISOMERASE ARE PROBABLY IDENTICAL PROTEINS [J].
FISCHER, G ;
WITTMANNLIEBOLD, B ;
LANG, K ;
KIEFHABER, T ;
SCHMID, FX .
NATURE, 1989, 337 (6206) :476-478
[7]  
FISCHER G, 1990, NATURE, V29, P813
[8]  
FISCHER G, 1990, BIOCHEMISTRY-US, V29, P813
[9]   YEAST CYCLOPHILIN - ISOLATION AND CHARACTERIZATION OF THE PROTEIN, CDNA AND GENE [J].
HAENDLER, B ;
KELLER, R ;
HIESTAND, PC ;
KOCHER, HP ;
WEGMANN, G ;
MOVVA, NR .
GENE, 1989, 83 (01) :39-46
[10]  
HANDLER B, 1987, EMBO J, V6, P947