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Investigation of the Molybdenum Cofactor through Chemical, Biochemical and Biophysical Studies

通过化学、生物化学和生物物理研究研究钼辅因子

基本信息

批准号：
10046549
负责人：
PARTHA BASU
金额：
$ 46.48万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10046549
关键词：
Aldehyde oxidase Amino Acids Aspartate Biochemical Cessation of life Chemicals Chemistry Coenzymes Combined molybdoflavoprotein enzyme deficiency Complement Complex Coupling Crystallography Cysteine Diamines Dimethyl Sulfoxide Disease Dissociation Distress Disulfide Linkage Electron Spin Resonance Spectroscopy Electron Transport Electrons Environment Enzymes Failure Family Gastrointestinal tract structure Health Human Investigation Kinetics Knowledge Life Ligands Mass Spectrum Analysis Metals Modeling Molecular Monitor Nitrate Reductases Nitrates Oxidants Oxidation-Reduction Oxides Oxidoreductase Physiological Process Property Proteins Pterins Pyrans Reaction Research Roentgen Rays Sampling Selenocysteine Serine Spectrum Analysis Structure Sulfhydryl Compounds Techniques Testing Time Variant Work X-Ray Crystallography Xanthine Oxidase absorption biophysical analysis chemical property chemical synthesis cofactor density dimethyl sulfoxide reductase early childhood electron donor electronic structure experimental study geometric structure member microorganism molybdenum cofactor oxidation periplasm prototype pyranopterin respiratory spectroscopic survey success sulfite oxidase theories trimethyloxamine

项目摘要

Title: Investigation of the Molybdenum Cofactor through Chemical, Biochemical and Biophysical Studies. Molybdenum cofactor (Moco) is an essential biomolecule for life. Numerous enzymes rely on proper functioning of Moco and failure to biosynthesize Moco causes severe physiological distress and early childhood death. Outside the protein environment, this cofactor is unstable and has not yet been synthesized chemically. Moco has several redox active components and, together, these components can carry out up to ten-electron chemistry, while substrate transformation requires only two electrons. To understand how different components stabilize the electronic structure that supports reactivity, we will investigate discrete molecules with defined features. The work outlined in this proposal seeks to complete the first chemical synthesis of Moco. While in the reduced state Moco is unstable outside the protein environment, and how it is stabilized within a protein is not clear. The proposal also seeks to understand geometric properties of Moco in the DMSO reductase family of enzymes using periplasmic nitrate reductase (NapA) and its variants as a model through biochemical and biophysical studies. The specific aims of the proposal are: 1) to synthesize pterin Mo-centers and Mo=X (X=S,O) complexes allowing investigation of their geometric and electronic structures in relation to reactivity; 2) understanding the geometric and functional properties of the Mo-center in the DMSOR family using NapA as a model. Overall, new important molecular level knowledge will be generated about the structure-function for a class of enzymes important to human health.

题目：钼辅助因子的化学、生化和生物物理研究。