STRUCTURAL ANALYSIS OF METHYLKETONE SYNTHASE 1

甲基酮合酶1的结构分析

• 批准号: 7370689
• 负责人: Michele E Auldridge
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7370689
• 关键词: STRUCTURAL; ANALYSIS; METHYLKETONE; SYNTHASE

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. Medium length methylketones like 2-tridecanone and 2-undecanone are potent toxins to a number of herbivorous insects. The production of both 2-tridecanone and 2-undecanone was recently linked to the expression of a member of the ?/? hydrolase fold family of proteins, Methylketone Sythase 1 (MKS1). MKS1 is a plastid localized protein shown to catalyze the de-esterification of ?-myristoyl-ACP to ?-ketoacids. Proteins containing the ?/? hydrolase fold have little sequence identity but do possess a conserved catalytic triad of nucleophile, acid and a histidine in their active sites. Typically these residues consist of Ser, Asp, and His. Upon modeling MKS1 from Hydroxynitrile Lysase (HNL), also a member of the ?/? hydrolase superfamily, it was apparent that MKS1 did not contain the canonical catalytic triad. MKS1 crystals were obtained and the three deminsional structure was solved at 2.3 ¿¿resolution by molecular replacement using HNL. From the crystal structure a highly stable H2O molecule was present within the MKS1 active site leading to the proposal that this H2O molecule could act as the nucleophile missing in MKS1. In order to address the proposed mechanism, higher resolution data of MKS1 in complex with substrate and or products is a requirement.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。中等长度的甲基酮，如 2-十三酮和 2-十一酮，对许多草食性昆虫来说是强效毒素。最近，2-十三酮和2-十一酮的产生与α/β成员的表达相关。蛋白质水解酶折叠家族，甲基酮 Sythase 1 (MKS1)。 MKS1 是一种质体定位蛋白，可催化 β-肉豆蔻酰-ACP 去酯化为 β-酮酸。含有 ?/? 的蛋白质水解酶折叠几乎没有序列同一性，但在其活性位点确实具有亲核试剂、酸和组氨酸的保守催化三联体。通常这些残基由 Ser、Asp 和 His 组成。根据羟基腈裂解酶 (HNL) 对 MKS1 进行建模，该酶也是 ?/? 的成员。水解酶超家族中，很明显 MKS1 不包含典型的催化三联体。获得了 MKS1 晶体，并通过 HNL 分子置换以 2.3 英寸分辨率解析了三维结构。从晶体结构来看，MKS1 活性位点内存在高度稳定的 H2O 分子，因此有人提出该 H2O 分子可以充当 MKS1 中缺失的亲核试剂。为了解决所提出的机制，需要更高分辨率的 MKS1 与底物和/或产物复合物的数据。