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THE 2.2-A RESOLUTION X-RAY CRYSTAL-STRUCTURE OF THE COMPLEX OF TRYPSIN INHIBITED BY 4-CHLORO-3-ETHOXY-7-GUANIDINOISOCOUMARIN - A PROPOSED MODEL OF THE THROMBIN INHIBITOR COMPLEX
被引:31
作者
:
CHOW, MM
论文数:
0
引用数:
0
h-index:
0
机构:
TEXAS A&M UNIV SYST,DEPT BIOCHEM & BIOPHYS,COLLEGE STN,TX 77843
CHOW, MM
MEYER, EF
论文数:
0
引用数:
0
h-index:
0
机构:
TEXAS A&M UNIV SYST,DEPT BIOCHEM & BIOPHYS,COLLEGE STN,TX 77843
MEYER, EF
BODE, W
论文数:
0
引用数:
0
h-index:
0
机构:
TEXAS A&M UNIV SYST,DEPT BIOCHEM & BIOPHYS,COLLEGE STN,TX 77843
BODE, W
KAM, CM
论文数:
0
引用数:
0
h-index:
0
机构:
TEXAS A&M UNIV SYST,DEPT BIOCHEM & BIOPHYS,COLLEGE STN,TX 77843
KAM, CM
RADHAKRISHNAN, R
论文数:
0
引用数:
0
h-index:
0
机构:
TEXAS A&M UNIV SYST,DEPT BIOCHEM & BIOPHYS,COLLEGE STN,TX 77843
RADHAKRISHNAN, R
VIJAYALAKSHMI, J
论文数:
0
引用数:
0
h-index:
0
机构:
TEXAS A&M UNIV SYST,DEPT BIOCHEM & BIOPHYS,COLLEGE STN,TX 77843
VIJAYALAKSHMI, J
POWERS, JC
论文数:
0
引用数:
0
h-index:
0
机构:
TEXAS A&M UNIV SYST,DEPT BIOCHEM & BIOPHYS,COLLEGE STN,TX 77843
POWERS, JC
机构
:
[1]
TEXAS A&M UNIV SYST,DEPT BIOCHEM & BIOPHYS,COLLEGE STN,TX 77843
[2]
MAX PLANCK INST BIOCHEM,W-8033 MARTINSRIED,GERMANY
[3]
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
来源
:
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
|
1990年
/ 112卷
/ 21期
关键词
:
D O I
:
10.1021/ja00177a045
中图分类号
:
O6 [化学];
学科分类号
:
0703 ;
摘要
:
The crystal structure of trypsin complexed to 4-chloro-3-ethoxy-7-guanidinoisocoumarin, a potent, irreversible inhibitor of both trypsin and thrombin, has been determined to 2.20-Å resolution and refined to an R factor of 0.15 by a geometric restraint least-squares procedure. The results provide positive structural evidence for a mechanism of irreversible inactivation of the enzyme via a quinone imine methide intermediate to form a covalent adduct with the active-site His-57 residue. The chloro acyl enzyme intermediate at Ser-195 is also present. H-bonding interactions formed in the active-site complex by both inhibitor models are summarized. The structures of the complexes of 4-chloro-3-ethoxy-7-guanidinoisocoumarin with porcine pancreatic elastase and bovine trypsin have been compared, and clearly their structures are quite different. Binding conformations of this isocoumarin inhibitor are modeled by active-site homology into the structure of human α-thrombin, which is an enzyme of pharmacological interest and whose structure has recently been solved. © 1990, American Chemical Society. All rights reserved.
引用
收藏
页码:7783 / 7789
页数:7
相关论文
共 23 条
[1]
REFINED CRYSTAL-STRUCTURE OF BOVINE BETA-TRYPSIN AT 1.8 A RESOLUTION .2. CRYSTALLOGRAPHIC REFINEMENT, CALCIUM-BINDING SITE, BENZAMIDINE BINDING-SITE AND ACTIVE-SITE AT PH 7.0
BODE, W
论文数:
0
引用数:
0
h-index:
0
机构:
MAX PLANCK INST BIOCHEM,8033 MARTINSRIED,FED REP GER
BODE, W
SCHWAGER, P
论文数:
0
引用数:
0
h-index:
0
机构:
MAX PLANCK INST BIOCHEM,8033 MARTINSRIED,FED REP GER
SCHWAGER, P
[J].
JOURNAL OF MOLECULAR BIOLOGY,
1975,
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717
[2]
THE REFINED 1.9 A CRYSTAL-STRUCTURE OF HUMAN ALPHA-THROMBIN - INTERACTION WITH D-PHE-PRO-ARG CHLOROMETHYLKETONE AND SIGNIFICANCE OF THE TYR-PRO-PRO-TRP INSERTION SEGMENT
BODE, W
论文数:
0
引用数:
0
h-index:
0
机构:
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
BODE, W
MAYR, I
论文数:
0
引用数:
0
h-index:
0
机构:
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
MAYR, I
BAUMANN, U
论文数:
0
引用数:
0
h-index:
0
机构:
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
BAUMANN, U
HUBER, R
论文数:
0
引用数:
0
h-index:
0
机构:
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
HUBER, R
STONE, SR
论文数:
0
引用数:
0
h-index:
0
机构:
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
STONE, SR
HOFSTEENGE, J
论文数:
0
引用数:
0
h-index:
0
机构:
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
HOFSTEENGE, J
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HUMAN-LEUKOCYTE AND PORCINE PANCREATIC ELASTASE - X-RAY CRYSTAL-STRUCTURES, MECHANISM, SUBSTRATE-SPECIFICITY, AND MECHANISM-BASED INHIBITORS
BODE, W
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
BODE, W
MEYER, E
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
MEYER, E
POWERS, JC
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
POWERS, JC
[J].
BIOCHEMISTRY,
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[4]
3-ALKOXY-7-AMINO-4-CHLOROISOCOUMARINS - A NEW CLASS OF SUICIDE SUBSTRATES FOR SERINE PROTEASES
HARPER, JW
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
HARPER, JW
POWERS, JC
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
POWERS, JC
[J].
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,
1984,
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: 7618
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7619
[5]
REACTION OF SERINE PROTEASES WITH SUBSTITUTED 3-ALKOXY-4-CHLOROISOCOUMARINS AND 3-ALKOXY-7-AMINO-4-CHLOROISOCOUMARINS - NEW REACTIVE MECHANISM-BASED INHIBITORS
HARPER, JW
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
HARPER, JW
POWERS, JC
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
POWERS, JC
[J].
BIOCHEMISTRY,
1985,
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7213
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STRUCTURAL BASIS OF ACTIVATION AND ACTION OF TRYPSIN
HUBER, R
论文数:
0
引用数:
0
h-index:
0
HUBER, R
BODE, W
论文数:
0
引用数:
0
h-index:
0
BODE, W
[J].
ACCOUNTS OF CHEMICAL RESEARCH,
1978,
11
(03)
: 114
-
122
[7]
GRAPHICS MODEL-BUILDING AND REFINEMENT SYSTEM FOR MACROMOLECULES
JONES, TA
论文数:
0
引用数:
0
h-index:
0
JONES, TA
[J].
JOURNAL OF APPLIED CRYSTALLOGRAPHY,
1978,
11
(AUG)
: 268
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[8]
MECHANISM-BASED ISOCOUMARIN INHIBITORS FOR TRYPSIN AND BLOOD-COAGULATION SERINE PROTEASES - NEW ANTICOAGULANTS
KAM, CM
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,DEPT CHEM,ATLANTA,GA 30332
KAM, CM
FUJIKAWA, K
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,DEPT CHEM,ATLANTA,GA 30332
FUJIKAWA, K
POWERS, JC
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,DEPT CHEM,ATLANTA,GA 30332
POWERS, JC
[J].
BIOCHEMISTRY,
1988,
27
(07)
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-
2557
[9]
KENNARD O, 1972, MOL STRUCTURES DIM A, V1
[10]
REVISED ANALYTIC CONSTANTS FOR ATOMIC SCATTERING FACTORS
LEE, JD
论文数:
0
引用数:
0
h-index:
0
LEE, JD
PAKES, HW
论文数:
0
引用数:
0
h-index:
0
PAKES, HW
[J].
ACTA CRYSTALLOGRAPHICA SECTION A-CRYSTAL PHYSICS DIFFRACTION THEORETICAL AND GENERAL CRYSTALLOGRAPHY,
1969,
A 25
: 712
-
&
←
1
2
3
→
共 23 条
[1]
REFINED CRYSTAL-STRUCTURE OF BOVINE BETA-TRYPSIN AT 1.8 A RESOLUTION .2. CRYSTALLOGRAPHIC REFINEMENT, CALCIUM-BINDING SITE, BENZAMIDINE BINDING-SITE AND ACTIVE-SITE AT PH 7.0
BODE, W
论文数:
0
引用数:
0
h-index:
0
机构:
MAX PLANCK INST BIOCHEM,8033 MARTINSRIED,FED REP GER
BODE, W
SCHWAGER, P
论文数:
0
引用数:
0
h-index:
0
机构:
MAX PLANCK INST BIOCHEM,8033 MARTINSRIED,FED REP GER
SCHWAGER, P
[J].
JOURNAL OF MOLECULAR BIOLOGY,
1975,
98
(04)
: 693
-
717
[2]
THE REFINED 1.9 A CRYSTAL-STRUCTURE OF HUMAN ALPHA-THROMBIN - INTERACTION WITH D-PHE-PRO-ARG CHLOROMETHYLKETONE AND SIGNIFICANCE OF THE TYR-PRO-PRO-TRP INSERTION SEGMENT
BODE, W
论文数:
0
引用数:
0
h-index:
0
机构:
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
BODE, W
MAYR, I
论文数:
0
引用数:
0
h-index:
0
机构:
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
MAYR, I
BAUMANN, U
论文数:
0
引用数:
0
h-index:
0
机构:
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
BAUMANN, U
HUBER, R
论文数:
0
引用数:
0
h-index:
0
机构:
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
HUBER, R
STONE, SR
论文数:
0
引用数:
0
h-index:
0
机构:
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
STONE, SR
HOFSTEENGE, J
论文数:
0
引用数:
0
h-index:
0
机构:
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
FRIEDRICH MIESCHER INST, CH-4002 BASEL, SWITZERLAND
HOFSTEENGE, J
[J].
EMBO JOURNAL,
1989,
8
(11)
: 3467
-
3475
[3]
HUMAN-LEUKOCYTE AND PORCINE PANCREATIC ELASTASE - X-RAY CRYSTAL-STRUCTURES, MECHANISM, SUBSTRATE-SPECIFICITY, AND MECHANISM-BASED INHIBITORS
BODE, W
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
BODE, W
MEYER, E
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
MEYER, E
POWERS, JC
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
POWERS, JC
[J].
BIOCHEMISTRY,
1989,
28
(05)
: 1951
-
1963
[4]
3-ALKOXY-7-AMINO-4-CHLOROISOCOUMARINS - A NEW CLASS OF SUICIDE SUBSTRATES FOR SERINE PROTEASES
HARPER, JW
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
HARPER, JW
POWERS, JC
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
POWERS, JC
[J].
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,
1984,
106
(24)
: 7618
-
7619
[5]
REACTION OF SERINE PROTEASES WITH SUBSTITUTED 3-ALKOXY-4-CHLOROISOCOUMARINS AND 3-ALKOXY-7-AMINO-4-CHLOROISOCOUMARINS - NEW REACTIVE MECHANISM-BASED INHIBITORS
HARPER, JW
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
HARPER, JW
POWERS, JC
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
GEORGIA INST TECHNOL,SCH CHEM,ATLANTA,GA 30332
POWERS, JC
[J].
BIOCHEMISTRY,
1985,
24
(25)
: 7200
-
7213
[6]
STRUCTURAL BASIS OF ACTIVATION AND ACTION OF TRYPSIN
HUBER, R
论文数:
0
引用数:
0
h-index:
0
HUBER, R
BODE, W
论文数:
0
引用数:
0
h-index:
0
BODE, W
[J].
ACCOUNTS OF CHEMICAL RESEARCH,
1978,
11
(03)
: 114
-
122
[7]
GRAPHICS MODEL-BUILDING AND REFINEMENT SYSTEM FOR MACROMOLECULES
JONES, TA
论文数:
0
引用数:
0
h-index:
0
JONES, TA
[J].
JOURNAL OF APPLIED CRYSTALLOGRAPHY,
1978,
11
(AUG)
: 268
-
272
[8]
MECHANISM-BASED ISOCOUMARIN INHIBITORS FOR TRYPSIN AND BLOOD-COAGULATION SERINE PROTEASES - NEW ANTICOAGULANTS
KAM, CM
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,DEPT CHEM,ATLANTA,GA 30332
KAM, CM
FUJIKAWA, K
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,DEPT CHEM,ATLANTA,GA 30332
FUJIKAWA, K
POWERS, JC
论文数:
0
引用数:
0
h-index:
0
机构:
GEORGIA INST TECHNOL,DEPT CHEM,ATLANTA,GA 30332
POWERS, JC
[J].
BIOCHEMISTRY,
1988,
27
(07)
: 2547
-
2557
[9]
KENNARD O, 1972, MOL STRUCTURES DIM A, V1
[10]
REVISED ANALYTIC CONSTANTS FOR ATOMIC SCATTERING FACTORS
LEE, JD
论文数:
0
引用数:
0
h-index:
0
LEE, JD
PAKES, HW
论文数:
0
引用数:
0
h-index:
0
PAKES, HW
[J].
ACTA CRYSTALLOGRAPHICA SECTION A-CRYSTAL PHYSICS DIFFRACTION THEORETICAL AND GENERAL CRYSTALLOGRAPHY,
1969,
A 25
: 712
-
&
←
1
2
3
→