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

页码：626 / 631

页数：6

共 33 条

[1] SOLVENT VISCOSITY AND PROTEIN DYNAMICS [J].

BEECE, D ;

EISENSTEIN, L ;

FRAUENFELDER, H ;

GOOD, D ;

MARDEN, MC ;

REINISCH, L ;

REYNOLDS, AH ;

SORENSEN, LB ;

YUE, KT .

BIOCHEMISTRY, 1980, 19 (23) :5147-5157

[2] CRYSTALLOGRAPHIC R-FACTOR REFINEMENT BY MOLECULAR-DYNAMICS [J].

BRUNGER, AT ;

KURIYAN, J ;

KARPLUS, M .

SCIENCE, 1987, 235 (4787) :458-460

[3] SOLVENT-ACCESSIBLE SURFACES OF PROTEINS AND NUCLEIC-ACIDS [J].

CONNOLLY, ML .

SCIENCE, 1983, 221 (4612) :709-713

[4] CRYSTAL-STRUCTURE OF NITRIC-OXIDE INHIBITED CYTOCHROME-C PEROXIDASE [J].

EDWARDS, SL ;

KRAUT, J ;

POULOS, TL .

BIOCHEMISTRY, 1988, 27 (21) :8074-8081

[5] A CAVITY-CONTAINING MUTANT OF T4 LYSOZYME IS STABILIZED BY BURIED BENZENE [J].

ERIKSSON, AE ;

BAASE, WA ;

WOZNIAK, JA ;

MATTHEWS, BW .

NATURE, 1992, 355 (6358) :371-373

[6] RESPONSE OF A PROTEIN-STRUCTURE TO CAVITY-CREATING MUTATIONS AND ITS RELATION TO THE HYDROPHOBIC EFFECT [J].

ERIKSSON, AE ;

BAASE, WA ;

ZHANG, XJ ;

HEINZ, DW ;

BLABER, M ;

BALDWIN, EP ;

MATTHEWS, BW .

SCIENCE, 1992, 255 (5041) :178-183

[7] SIMILAR HYDROPHOBIC REPLACEMENTS OF LEU99 AND PHE153 WITHIN THE CORE OF T4-LYSOZYME HAVE DIFFERENT STRUCTURAL AND THERMODYNAMIC CONSEQUENCES [J].

ERIKSSON, AE ;

BAASE, WA ;

MATTHEWS, BW .

JOURNAL OF MOLECULAR BIOLOGY, 1993, 229 (03) :747-769

[8] DETECTION OF AN OXYFERRYL PORPHYRIN PI-CATION-RADICAL INTERMEDIATE IN THE REACTION BETWEEN HYDROGEN-PEROXIDE AND A MUTANT YEAST CYTOCHROME-C PEROXIDASE - EVIDENCE FOR TRYPTOPHAN-191 INVOLVEMENT IN THE RADICAL SITE OF COMPOUND-I [J].

ERMAN, JE ;

VITELLO, LB ;

MAURO, JM ;

KRAUT, J .

BIOCHEMISTRY, 1989, 28 (20) :7992-7995

[9] DYNAMICS OF A FLEXIBLE LOOP IN DIHYDROFOLATE-REDUCTASE FROM ESCHERICHIA-COLI AND ITS IMPLICATION FOR CATALYSIS [J].

FALZONE, CJ ;

WRIGHT, PE ;

BENKOVIC, SJ .

BIOCHEMISTRY, 1994, 33 (02) :439-442

[10] THE ROLE OF ASPARTATE-235 IN THE BINDING OF CATIONS TO AN ARTIFICIAL CAVITY AT THE RADICAL SITE OF CYTOCHROME-C PEROXIDASE [J].

FITZGERALD, MM ;

TRESTER, ML ;

JENSEN, GM ;

MCREE, DE ;

GOODIN, DB .

PROTEIN SCIENCE, 1995, 4 (09) :1844-1850

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