Substrate Channeling and Communication in Proline Metabolic Enzymes

脯氨酸代谢酶中的底物通道和通讯

• 批准号: 10658203
• 负责人: Donald F Becker
• 金额: $ 45.65万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-05 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658203
• 关键词: 3-Dimensional; Active Sites; Address; Architecture; Binding; Biological Process; Biophysics; Catabolism; Cells; Cellular Structures; Communication; Cryoelectron Microscopy; Crystallography; Data; Deposition; Development; Disease; Electrons; Enzymatic Biochemistry; Enzymes; Evolution; Flavins; Funding; Genes; Glutamates; Goals; Health; Hereditary Disease; Human; Hydrolysis; Infection; Inherited; Insecta; Ions; Kinetics; Knowledge; Larva; Length; Malignant Neoplasms; Mediating; Metabolic; Metabolic Diseases; Metabolic Pathway; Metabolism; Molecular; Molecular Conformation; Multienzyme Complexes; Mutation; Nature; Nematoda; Organism; Output; Oxidation-Reduction; Oxidoreductase; Pathogenesis; Pathway interactions; Phase; Phenotype; Physiological; Play; Productivity; Proline; Proline Dehydrogenase; Protein Conformation; Proteins; Publications; Regulon; Request for Applications; Research; Resolution; Roentgen Rays; Role; Side; Signal Transduction; Signaling Molecule; Site; Structure; System; Time; Transcription Repressor; Virulence; Xenorhabdus luminescens; aldehyde dehydrogenases; bacterial fitness; carboxylate; carboxylation; chemical reaction; electron density; enzyme mechanism; experimental study; flexibility; member; mutant; novel; oxidation; pathogen; proline permease; protective pathway; protein protein interaction; pyrroline; structural biology; symbiont

PROJECT SUMMARY Metabolic enzymes in cells rarely function in isolation. Often their activities are coordinated by physical or covalent association with each other and cellular structures. A consequence of these associations is that metabolic intermediates do not equilibrate with the cellular milieu and are instead channeled between enzyme active sites. Despite the widespread recognition that protein-protein interactions are ubiquitous, the molecular mechanisms of substrate channeling remain obscure, and the impact of channeling at the cellular and organismal levels is largely unknown. We seek to narrow these knowledge gaps by exploring substrate channeling within and between the enzymes of proline catabolism. The proposed experiments will explore long-distance, allosteric communication between the active sites of the bifunctional enzyme PutA using kinetic crystallography, assess the contributions of substrate channeling to bacterial fitness and pathogenesis, and determine the first structure of a novel bifunctional enzyme that moonlights as a transcriptional repressor using cryo-EM.

项目摘要 细胞中的代谢酶很少单独起作用。他们的活动往往是由身体或 与彼此和细胞结构的共价缔合。这些联系的结果是， 代谢中间产物不会与细胞环境平衡，而是在细胞之间流动 酶活性位点尽管人们普遍认为蛋白质-蛋白质相互作用是普遍存在的， 基质沟道的分子机制仍然不清楚，并且沟道在 细胞和有机体水平在很大程度上是未知的。我们试图通过探索缩小这些知识差距 脯氨酸催化剂酶内和酶间的底物通道。拟议的实验 将探索双功能酶活性位点之间的长距离变构通讯 PutA使用动力学晶体学，评估底物通道对细菌适应性的贡献 和发病机制，并确定了一种新型双功能酶的第一个结构， 使用cryo-EM检测转录抑制因子。

项目成果

Structural basis of substrate selectivity of Δ(1)-pyrroline-5-carboxylate dehydrogenase (ALDH4A1): semialdehyde chain length.

• DOI: 10.1016/j.abb.2013.07.024
• 发表时间: 2013-10-01
• 期刊: ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
• 影响因子: 3.9
• 作者: Pemberton, Travis A.;Tanner, John J.
• 通讯作者: Tanner, John J.

Probing the function of a ligand-modulated dynamic tunnel in bifunctional proline utilization A (PutA).

• DOI: 10.1016/j.abb.2021.109025
• 发表时间: 2021-11-15
• 期刊: Archives of biochemistry and biophysics
• 影响因子: 3.9
• 作者: Korasick DA;Christgen SL;Qureshi IA;Becker DF;Tanner JJ
• 通讯作者: Tanner JJ

Redox-induced changes in flavin structure and roles of flavin N(5) and the ribityl 2'-OH group in regulating PutA--membrane binding.

氧化还原诱导的黄素结构变化以及黄素 N(5) 和 ribityl 2-OH 基团在调节 PutA-膜结合中的作用。

• DOI: 10.1021/bi061935g
• 发表时间: 2007
• 期刊: Biochemistry
• 影响因子: 2.9
• 作者: Zhang,Weimin;Zhang,Min;Zhu,Weidong;Zhou,Yuzhen;Wanduragala,Srimevan;Rewinkel,Dustin;Tanner,JohnJ;Becker,DonaldF
• 通讯作者: Becker,DonaldF

Structural basis of the transcriptional regulation of the proline utilization regulon by multifunctional PutA.

• DOI: 10.1016/j.jmb.2008.05.084
• 发表时间: 2008-08
• 期刊: Journal of molecular biology
• 影响因子: 5.6
• 作者: Yuzhen Zhou;J. D. Larson;C. Bottoms;E. Arturo;M. Henzl;J. Jenkins;J. Nix;D. Becker;J. Tanner

Structure, function, and mechanism of proline utilization A (PutA).

• DOI: 10.1016/j.abb.2017.07.005
• 发表时间: 2017-10-15
• 期刊: Archives of biochemistry and biophysics
• 影响因子: 3.9
• 作者: Liu LK;Becker DF;Tanner JJ
• 通讯作者: Tanner JJ