CRYSTAL-STRUCTURE OF A PENTAMIDINE OLIGONUCLEOTIDE COMPLEX - IMPLICATIONS FOR DNA-BINDING PROPERTIES

被引：185

作者：

EDWARDS, KJ ^{[1
]}

JENKINS, TC ^{[1
]}

NEIDLE, S ^{[1
]}

机构：

[1] INST CANC RES,CANC RES CAMPAIGN BIOMOLEC STRUCT UNIT,SUTTON SM2 5NG,SURREY,ENGLAND

来源：

BIOCHEMISTRY | 1992年 / 31卷 / 31期

关键词：

D O I：

10.1021/bi00146a011

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：

The crystal structure of the complex formed between the dodecanucleotide d(CGCGAATTCGCG)2 and the drug pentamidine, which is active against the Pneumocystis carinii pathogen in AIDS patients, has been determined to a resolution of 2.1 angstrom and an R-factor of 19.4%. Analysis of the structure has shown the drug to be bound in the 5'-AATT minor groove region of the duplex, with the amidinium groups H-bonded to adenine N3 atoms in an interstrand manner. The drug molecule adopts an extended conformation, and the immediate binding site spans four base pairs. Structural details of the drug-DNA interactions are discussed, and comparison is made with the dodecamer complex of the structurally similar berenil ligand.

引用

页码：7104 / 7109

页数：6

共 32 条

[1] STRUCTURE-ACTIVITY-RELATIONSHIPS OF ANALOGS OF PENTAMIDINE AGAINST PLASMODIUM-FALCIPARUM AND LEISHMANIA-MEXICANA-AMAZONENSIS
BELL, CA
HALL, JE
KYLE, DE
GROGL, M
OHEMENG, KA
ALLEN, MA
TIDWELL, RR
[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1990, 34 (07) : 1381 - 1386
[2] CRYSTAL-STRUCTURE OF A BERENIL DODECANUCLEOTIDE COMPLEX - THE ROLE OF WATER IN SEQUENCE-SPECIFIC LIGAND-BINDING
BROWN, DG
SANDERSON, MR
SKELLY, JV
JENKINS, TC
BROWN, T
GARMAN, E
STUART, DI
NEIDLE, S
[J]. EMBO JOURNAL, 1990, 9 (04) : 1329 - 1334
[3] BROWN DG, 1992, IN PRESS J MOL BIOL
[4] MOLECULAR-STRUCTURE OF THE NETROPSIN-D(CGCGATATCGCG) COMPLEX - DNA CONFORMATION IN AN ALTERNATING AT SEGMENT
COLL, M
AYMAMI, J
VANDERMAREL, GA
VANBOOM, JH
RICH, A
WANG, AHJ
[J]. BIOCHEMISTRY, 1989, 28 (01) : 310 - 320
[5] STRUCTURE AND DNA-BINDING ACTIVITY OF ANALOGS OF 1,5-BIS(4-AMIDINOPHENOXY)PENTANE (PENTAMIDINE)
CORY, M
TIDWELL, RR
FAIRLEY, TA
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (03) : 431 - 438
[6] DECLERCQ E, 1990, J MED CHEM, V23, P787
[7] DESIGN OF SEQUENCE-SPECIFIC DNA-BINDING MOLECULES
DERVAN, PB
[J]. SCIENCE, 1986, 232 (4749) : 464 - 471
[8] STRUCTURE OF A B-DNA DODECAMER .2. INFLUENCE OF BASE SEQUENCE ON HELIX STRUCTURE
DICKERSON, RE
DREW, HR
[J]. JOURNAL OF MOLECULAR BIOLOGY, 1981, 149 (04) : 761 - 786
[9] STRUCTURE OF A B-DNA DODECAMER .3. GEOMETRY OF HYDRATION
DREW, HR
DICKERSON, RE
[J]. JOURNAL OF MOLECULAR BIOLOGY, 1981, 151 (03) : 535 - 556
[10] FOOTPRINTING STUDIES ON THE SEQUENCE-SELECTIVE BINDING OF PENTAMIDINE TO DNA
FOX, KR
SANSOM, CE
STEVENS, MFG
[J]. FEBS LETTERS, 1990, 266 (1-2) : 150 - 154

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