ACTIVE SITES OF CREATINE KINASE FROM HEART & MUSCLE

心脏肌酸激酶的活性位点

• 批准号: 6456669
• 负责人: PATRICIA CLEMENT BABBITT
• 金额: $ 27.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6456669
• 关键词: bacteria; bioengineering /biomedical engineering; biomedical resource; plants

Creatine kinase (CK) is an enzyme involved in the regulation of energy levels in the cell. It has clinically important functions in the cardiovascular system and is being investigated in association with development, hormone regulation of a range of physiological functions, and disease states ranging from neuromuscular disorders to cancer. We are studying its structure-function relationships. We are using two structures of creatine kinases and one of a homolog, arginine kinase, to better interpret the structure-function relationships in CK and other guanidino kinases and require the resources of the Computer Graphics Laboratory to visualize and compare these structures. We build models to reflect structural differences among the CK isoenzymes and use those models to help us understand how these forms evolved to interact with different cellular structures. Integration of structural and mechanistic information in this fashion reflects the major focus of our studies. The Computer Graphics Laboratory is central to the development of this line of inquiry. This system also serves as a model system for development of new computational tools to model structure-function relationships in collaboration with investigators outside of UCSF. Again, the CGL is critical to this effort and we plan collaborations with CGL staff to help us develop these tools for general use. We are currently using some new tools in development at CGL (MSFviewer and the associated superposition software, RmsMin) to map differences in specificity of CK isozyme sequences to the structural templates that are presently available. This exercise has helped us to predict additional putative active site residues initially identified from inverse folding computational experiments.

肌酸激酶（CK）是参与调节的酶 细胞中的能级。 它具有临床上重要的功能 心血管系统，正在研究 随着发育，一系列生理的激素调节 功能和疾病状态从神经肌肉疾病到 癌症。 我们正在研究其结构功能关系。 我们是 使用肌酸激酶的两个结构和一种同源物， 精氨酸激酶，更好地解释结构功能 CK和其他鸟养界激酶的关系，需要 计算机图形实验室的资源以可视化和比较 这些结构。 我们建立模型以反映结构差异 在CK同工酶中，并使用这些模型来帮助我们了解 这些形式演变为与不同的细胞结构相互作用。 以这种方式整合结构和机械信息 反映了我们研究的主要重点。 计算机图形 实验室对于这一探究线的发展至关重要。 该系统也是开发新的模型系统 计算工具来建模结构功能关系 与UCSF以外的调查员合作。 再次，CGL是 对这项努力至关重要，我们计划与CGL员工合作 帮助我们开发这些工具供一般使用。 我们目前正在使用 CGL开发的一些新工具（MSFViewer和关联的 叠加软件，rmsmin）以绘制特异性差异 CK同工酶序列到当前是结构模板的 可用的。 这项练习帮助我们预测了其他推定 最初从反折叠识别的活性位点残基 计算实验。