MOLECULAR INTERACTIONS AT THE CELL SURFACE
MOLECULAR INTERACTIONS AT THE CELL SURFACE
批准号:
3271099
负责人:
PAUL B SIGLER
金额:
$18.81万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1989
资助国家:
美国
项目状态:
已结题
起止时间:
1989-01-01 至 1990-12-31
关键词:
atomic absorption spectrometry calcium binding protein computer graphics /printing enzyme complex enzyme inhibitors enzyme substrate analog hormone binding protein hormone receptor membrane activity membrane lipids membrane proteins phospholipase A2 phospholipids stereochemistry steroid delta isomerase steroid hormone metabolism
中文摘要
结构/功能分析将继续进行蛋白质的相互作用
英文摘要
Structure/function analysis will continue on the interaction of proteins
with the surface of membranes and with steroids. Both processes figure
heavily in the control of intracellular metabolism; the former through the
enzymatic release of second mssengers from the cytosolic leaflet of the
plasma membrane; the later through steroid activation of genetic control
elements. Our principal tool will be high resolution crystallography of
the appropriate proteins and of their physiologically important complexes.
Phosphlipase A2 (PLA2) offers an ideal model for studying the interaction
of proteins with membrane surfaces since it prefers to attack phospholipid
head groups if they are in membranes or membrane-like aggregates. Despite
several high resolution crystal structures of PLA2 we do not yet understand
its action. To resolve this issue we will continue to systematically build
a stereochemical picture of the enzyme's functional interactions. The
steps are: (1) To complete the 1.7 A refinement of the ligand free form of
C. atrox PLA2; (2) To solve the high resolution crystal structure of the
calcium complex of C. atrox of PLA2; (3) To solve the high resolution
crystal structure of crotoxin, a phosphlipiasic neurotoxin whose action is
targeted to the presynaptic membrane; (4) To prepare crystals of PLA2 in
complexes with phosphlipid analogues that emulate the interaction between
PLA2 and phosphlipids in membrane-like aggregates. This requires the
synthesis of stable analogues in which the head groups are constrained to
resemble those in an aggregate, but that are small enough to cocrystallize
with the enzyme; (5) To explore the preparation of crystalline
intracellular phospholipases that mediate internal cell responses.
As a first model for protein steroid interaction, we will interpret the 2.5
A map of delta 5-KSI and contrast the structure with that of its
isomorphous steroid inhibitor complex. Once refined, these structures
should reveal the enzyme's mechanism of specific steroid binding and
catalysis. We hope to prepare crystals of the rather plentiful human sex
steroid binding globulin and ultimately to crystallize estrogen and
progesterone receptors.
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会议论文
CONSORTIUM FOR LARGE MACROMOLECULAR STRUCTURES
-
批准号:6667821
-
项目类别:
-
资助金额:$14.27万
-
财政年份:2002
-
负责人:PAUL B SIGLER
-
依托单位:
CONSORTIUM FOR LARGE MACROMOLECULAR STRUCTURES
-
批准号:6491144
-
项目类别:
-
资助金额:$14.27万
-
财政年份:2001
-
负责人:PAUL B SIGLER
-
依托单位:
CONSORTIUM FOR LARGE MACROMOLECULAR STRUCTURES
-
批准号:6339156
-
项目类别:
-
资助金额:$1.42万
-
财政年份:2000
-
负责人:PAUL B SIGLER
-
依托单位:
CONSORTIUM FOR LARGE MACROMOLECULAR STRUCTURES
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批准号:6220516
-
项目类别:
-
资助金额:$1.42万
-
财政年份:1999
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负责人:PAUL B SIGLER
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依托单位:
SPECIFIC PROTEIN DNA COMPLEXES TO STUDY CHEMICAL MECHANISM IN CELLULAR REG
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批准号:6120533
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项目类别:
-
资助金额:$0.02万
-
财政年份:1998
-
负责人:PAUL B SIGLER
-
依托单位:
SPECIFIC PROTEIN DNA COMPLEXES TO STUDY CHEMICAL MECHANISM IN CELLULAR REG
-
批准号:6281306
-
项目类别:
-
资助金额:$9.21万
-
财政年份:1998
-
负责人:PAUL B SIGLER
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依托单位:
HIGH RESOLUTION STUDIES OF SPECIFIC PROTEIN & PROTEIN & DNA COMPLEXES
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批准号:6251657
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项目类别:
-
资助金额:$1.12万
-
财政年份:1997
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负责人:PAUL B SIGLER
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依托单位:
MOLECULAR INTERACTIONS AT THE CELL SURFACE
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批准号:2173917
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项目类别:
-
资助金额:$22.51万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
STRUCTURAL ANALYSIS OF BIOLOGICAL MACROMOLECULES
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批准号:3484183
-
项目类别:
-
资助金额:$32.42万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
STRUCTURAL ANALYSIS OF BIOLOGICAL MACROMOLECULES
-
批准号:3268760
-
项目类别:
-
资助金额:$35.51万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
STRUCTURAL ANALYSIS OF BIOLOGICAL MACROMOLECULES
-
批准号:3268759
-
项目类别:
-
资助金额:$34.01万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
STRUCTURAL ANALYSIS OF BIOLOGICAL MACROMOLECULES
-
批准号:3484182
-
项目类别:
-
资助金额:$32.51万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
STRUCTURAL ANALYSIS OF BIOLOGICAL MACROMOLECULES
-
批准号:3484184
-
项目类别:
-
资助金额:$36.35万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
STRUCTURAL ANALYSIS OF BIOLOGICAL MACROMOLECULES
-
批准号:2518808
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项目类别:
-
资助金额:$40.7万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
MOLECULAR INTERACTIONS AT THE CELL SURFACE
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批准号:2173918
-
项目类别:
-
资助金额:$16.47万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
MOLECULAR INTERACTIONS AT THE CELL SURFACE
-
批准号:3271101
-
项目类别:
-
资助金额:$20.3万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
STRUCTURAL ANALYSIS OF BIOLOGICAL MACROMOLECULES
-
批准号:2169762
-
项目类别:
-
资助金额:$39.15万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
STRUCTURAL ANALYSIS OF BIOLOGICAL MACROMOLECULES
-
批准号:2169761
-
项目类别:
-
资助金额:$39.4万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
MOLECULAR INTERACTIONS AT THE CELL SURFACE
-
批准号:2173916
-
项目类别:
-
资助金额:$22.15万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
MOLECULAR INTERACTIONS AT THE CELL SURFACE
-
批准号:3271100
-
项目类别:
-
资助金额:$21.29万
-
财政年份:1989
-
负责人:PAUL B SIGLER
-
依托单位:
海外基金