A ligand-gated, hinged loop rearrangement opens a channel to a buried artificial protein cavity

被引:47
作者
Fitzgerald, MM [1 ]
Musah, RA [1 ]
McRee, DE [1 ]
Goodin, DB [1 ]
机构
[1] SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA
来源
NATURE STRUCTURAL BIOLOGY | 1996年 / 3卷 / 07期
关键词
D O I
10.1038/nsb0796-626
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
Conformational changes that gate the access of substrates or ligands to an active site are important features of enzyme function. In this report, we describe an unusual example of a structural rearrangement near a buried artificial cavity in cytochrome c peroxidase that occurs on binding protonated benzimidazole. A hinged main-chain rotation at two residues (Pro 190 and Asn 195) results in a surface loop rearrangement that opens a large solvent-accessible channel for the entry of ligands to an otherwise inaccessible binding site. The trapping of this alternate conformational state provides a unique view of the extent to which protein dynamics can allow small molecule penetration into buried protein cavities.
引用
收藏
页码:626 / 631
页数:6
相关论文
共 33 条
[21]   MODELING PROTEIN SUBSTRATE INTERACTIONS IN THE HEME DOMAIN OF CYTOCHROME P450(BM-3) [J].
LI, HY ;
POULOS, TL .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1995, 51 :21-32
[22]   FUNCTIONAL-ROLE OF A MOBILE LOOP OF ESCHERICHIA-COLI DIHYDROFOLATE-REDUCTASE IN TRANSITION-STATE STABILIZATION [J].
LI, LY ;
FALZONE, CJ ;
WRIGHT, PE ;
BENKOVIC, SJ .
BIOCHEMISTRY, 1992, 31 (34) :7826-7833
[23]  
McRee D.E., 1992, J. Mol. Graph, V10, P44
[24]   A CATION-BINDING MOTIF STABILIZES THE COMPOUND-I RADICAL OF CYTOCHROME-C PEROXIDASE [J].
MILLER, MA ;
HAN, GW ;
KRAUT, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (23) :11118-11122
[25]  
NOBBS CL, 1966, HEME HEMOPROTEINS, V1, P143
[26]   THE X-RAY CRYSTAL-STRUCTURE OF THE MEMBRANE-PROTEIN PROSTAGLANDIN-H(2) SYNTHASE-1 [J].
PICOT, D ;
LOLL, PJ ;
GARAVITO, RM .
NATURE, 1994, 367 (6460) :243-249
[27]   STRUCTURAL AND EVOLUTIONARY RELATIONSHIPS BETWEEN RETROVIRAL AND EUKARYOTIC ASPARTIC PROTEINASES [J].
RAO, JKM ;
ERICKSON, JW ;
WLODAWER, A .
BIOCHEMISTRY, 1991, 30 (19) :4663-4671
[28]   AMINO-ACID PREFERENCES FOR SPECIFIC LOCATIONS AT THE ENDS OF ALPHA-HELICES [J].
RICHARDSON, JS ;
RICHARDSON, DC .
SCIENCE, 1988, 240 (4859) :1648-1652
[29]   SEGMENTAL MOVEMENT - DEFINITION OF THE STRUCTURAL REQUIREMENTS FOR LOOP CLOSURE IN CATALYSIS BY TRIOSEPHOSPHATE ISOMERASE [J].
SAMPSON, NS ;
KNOWLES, JR .
BIOCHEMISTRY, 1992, 31 (36) :8482-8487
[30]  
SCHOLES CP, 1989, ISRAEL J CHEM, V29, P85