PROTEIN CARBOXYL METHYLATION IN BRAIN
PROTEIN CARBOXYL METHYLATION IN BRAIN
批准号:
6187707
负责人:
DANA WILLIAM ASWAD
金额:
$22.77万
依托单位国家:
美国
项目类别:
财政年份:
1981
资助国家:
美国
项目状态:
已结题
起止时间:
1981-04-01 至 2002-03-21
中文摘要
点击翻译按钮获取中文摘要
英文摘要
DESCRIPTION (Adapted from applicant's abstract): The overall goal of this
project is to elucidate the biological role of protein L-isoaspartyl
methyltransferase (PIMT), a protein methylating enzyme that is enriched in
brain and catalyzes selective methylation of atypical L-isoaspartyl
residues. These unusual structures are characterized by an abnormal
isopeptide bond in which an aspartyl residue is linked to its
carboxyl-flanking neighbor via its side-chain beta-carboxyl group, rather
than through the normal alpha-linkage. Isoaspartyl sites are believed to
arise from spontaneous alterations of proteins during aging and/or from
errors in protein synthesis. In vitro, PIMT has been demonstrated to
catalyze isoaspartate repair by converting beta-linkage to normal alpha
linkages. The aims of this continuation application are focused on two
areas: characterization of several proteins which appear to be important
targets of PIMT action in cells, and an attempt to demonstrate directly that
PIMT functions as a repair enzyme in vivo. This will be accomplished by
addressing 4 specific aims. The first will focus on histone H2B, a nuclear
protein recently shown to undergo a selective and dramatic increase in
isoaspartate content when PIMT activity is inhibited in rat PC12 cells. The
second will involve the purification and characterization of a recently
discovered high molecular weight methyl acceptor protein (HMAP) that is
found only in brain and appears to have an unusually high content of
isoaspartyl sites, as well as a high affinity for PIMT. The third specific
aim is to determine if synapsin-1, a protein involved in regulating the
availability of synaptic vesicles, forms isoaspartate in vivo. The final
aim is to characterize an unusual isoaspartate-rich protein in E. coli that
serves as an excellent substrate for rat brain PIMT. Together these
investigations should provide important new insights into the significance
of protein damage and repair systems in normal cell aging and in human
disease.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
FASEB Summer Research Conference-Biological Methylation
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批准号:6809748
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项目类别:
-
资助金额:$0.5万
-
财政年份:2004
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
FORMATION OF ISOASPARTATE IN PEPTIDES AND PROTEINS
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批准号:2267594
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项目类别:
-
资助金额:$10.9万
-
财政年份:1991
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负责人:DANA WILLIAM ASWAD
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依托单位:
FORMATION OF ISOASPARTATE IN PEPTIDES AND PROTEINS
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批准号:3416235
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项目类别:
-
资助金额:$12.15万
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财政年份:1991
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
FORMATION OF ISOASPARTATE IN PEPTIDES AND PROTEINS
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批准号:3416236
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项目类别:
-
资助金额:$10.34万
-
财政年份:1991
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
PROTEIN CARBOXYL METHYLATION AND NEURONAL FUNCTION
-
批准号:3074922
-
项目类别:
-
资助金额:$5.42万
-
财政年份:1986
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
PROTEIN CARBOXYL METHYLATION AND NEURONAL FUNCTION
-
批准号:3074924
-
项目类别:
-
资助金额:$5.73万
-
财政年份:1986
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
PROTEIN CARBOXYL METHYLATION AND NEURONAL FUNCTION
-
批准号:3074923
-
项目类别:
-
资助金额:$5.73万
-
财政年份:1986
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
PROTEIN CARBOXYL METHYLATION AND NEURONAL FUNCTION
-
批准号:3074926
-
项目类别:
-
资助金额:$5.63万
-
财政年份:1986
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
PROTEIN CARBOXYL METHYLATION AND NEURONAL FUNCTION
-
批准号:3074925
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项目类别:
-
资助金额:$5.58万
-
财政年份:1986
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负责人:DANA WILLIAM ASWAD
-
依托单位:
Protein Methylation in Brain
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批准号:6710584
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项目类别:
-
资助金额:$28.79万
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财政年份:1981
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负责人:DANA WILLIAM ASWAD
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依托单位:
Protein Damage and Repair in the Brain
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批准号:8089343
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项目类别:
-
资助金额:$25.64万
-
财政年份:1981
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
PROTEIN CARBOXYL METHYLATION IN BRAIN
-
批准号:3397449
-
项目类别:
-
资助金额:$13.18万
-
财政年份:1981
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
PROTEIN CARBOXYMETHYLATION IN BRAIN
-
批准号:2263166
-
项目类别:
-
资助金额:$20.81万
-
财政年份:1981
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
PROTEIN CARBOXYL METHYLATION IN BRAIN
-
批准号:3397450
-
项目类别:
-
资助金额:$16.23万
-
财政年份:1981
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
PROTEIN CARBOXYL METHYLATION IN BRAIN
-
批准号:3397448
-
项目类别:
-
资助金额:$12.5万
-
财政年份:1981
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
Protein Methylation in Brain
-
批准号:6860460
-
项目类别:
-
资助金额:$28.79万
-
财政年份:1981
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
PROTEIN CARBOXYMETHYLATION IN BRAIN
-
批准号:2263164
-
项目类别:
-
资助金额:$18.59万
-
财政年份:1981
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
PROTEIN CARBOXYMETHYLATION IN BRAIN
-
批准号:2263165
-
项目类别:
-
资助金额:$19.99万
-
财政年份:1981
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
Protein Damage and Repair in the Brain
-
批准号:7888186
-
项目类别:
-
资助金额:$25.95万
-
财政年份:1981
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
PROTEIN CARBOXYL METHYLATION IN BRAIN
-
批准号:3397447
-
项目类别:
-
资助金额:$5.85万
-
财政年份:1981
-
负责人:DANA WILLIAM ASWAD
-
依托单位:
海外基金