STRUCTURAL STUDIES ASSOCIATED WITH THE CATALYSIS OF FATTY ACID SYNTHASE

与脂肪酸合成酶催化相关的结构研究

• 批准号: 8169666
• 负责人: Francisco J Asturias
• 金额: $ 0.65万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169666
• 关键词: Animals; Architecture; Biochemical; Cardiovascular Diseases; Catalysis; Computer Retrieval of Information on Scientific Projects Database; Dimerization; Electron Microscopy; Embryonic Development; Fatty Acids; Fatty-acid synthase; Funding; Grant; Head; Homeostasis; Institution; Investigation; Location; Malignant Neoplasms; Modeling; Molecular Conformation; Obesity; Play; Publishing; Research; Research Personnel; Resources; Risk; Role; Source; Structure; United States National Institutes of Health; dimer; inhibitor/antagonist; particle; polypeptide

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Fatty acid synthase (FAS) catalyzes the de novo synthesis of fatty acids and plays an essential role in embryogenesis and energy homeostasis. Inhibitors of FAS have the potential as treamtents for obesity, thereby reducing the risk for related cardiovascular diseases, and for cancer. The animal cytosolic FAS is a 272 kDa multienzyme polypeptide that requires dimerization for activity. Biochemical evidence suggests that FAS subunits assume a coiled, head-to-head architecture. This model has been substantiated by our subsequent structural characterization of single FAS particles by electron microscopy (EM) and is consistent with a recently published crystal structure. However in both structures the carboxyl-terminal domains were not identified, consistent with their known conformational mobility. We propose to continue our investigations of FAS by EM to unequivocally determine locations of these mobile carboxyl terminal domains and to investigate the conformations assumed by the FAS dimer at each step in fatty acid synthesis.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 脂肪酸合酶（FAS）催化脂肪酸的从头合成，并在胚胎发生和能量稳态中起着至关重要的作用。 FAS的抑制剂具有作为肥胖症的Treamtents的潜力，从而降低了相关心血管疾病的风险和癌症的风险。 动物胞质FAS是272 kDa多酶多肽，需要二聚化才能进行活性。 生化证据表明，FAS亚基假设一个盘绕的，正面的建筑。 通过电子显微镜（EM）对单个FAS颗粒的后续结构表征，已经证实了该模型，并且与最近发表的晶体结构一致。 但是，在这两种结构中，羧基末端结构域均未鉴定，这与它们已知的构象迁移率一致。 我们建议继续通过EM对FAS进行研究，以明确确定这些移动羧基末端结构域的位置，并研究FAS二聚体在脂肪酸合成中每个步骤中假定的构象。