Refinement and Comparisons of the Structures of DAHPsynthases and KDOPsynthase

DAHP 合酶和 KDOP 合酶结构的精化和比较

• 批准号: 9723633
• 负责人: Robert Kretsinger
• 金额: $ 30万
• 依托单位: University of Virginia Main Campus
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9723633&HistoricalAwards=false
• 关键词: Refinement; Comparisons; Structures; DAHPsynthases; KDOPsynthase

9723633 Kretsinger The structures of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPsynthase) and 3-deoxy-D-manno-octulosonate-8-phosphate synthase (KDOPsynthase), will be determined by X-ray crystallography at atomic resolution, alone and in complex with substrates, inhibitors and regulators. The enzymes share 19% sequence identity and have secondary structures that resemble one another. The enzymes differ in their use of metal ions and regulation by feedback inhibition. Thus the ultimate goal of these studies is to determine the similarities and possible homologies between these enzymes. These enzymes catalyze the condensation of phosphoenol pyruvate with a sugar molecule containing four (erythrose-4-phosphate) and five (arabinose-5-phosphate) carbons, respectively. In both cases, an unusual cleavage occurs, in that the carbon-oxygen bond of phosphoenol pyruvate is cleaved and not the oxygen-phosphorus bond. Both enzymes are at important points of a biosynthetic pathway, one leading to aromatic end products, the other leading to the lipopolysaccharide of the outer membrane in Gram negative bacteria. The overall goal of this structural investigation by X-ray crystallography is to understand the similarities and differences in substrate binding and mechanisms of action of these two enzymes, and whether these two enzymes are homologues or have arisen by convergent evolution. ***

3-脱氧-d -阿拉伯-庚糖酸-7-磷酸合成酶（DAHPsynthase）和3-脱氧-d -甘露-辛基糖酸-8-磷酸合成酶（KDOPsynthase）的结构将通过x射线晶体学在原子分辨率下测定，可以单独测定，也可以与底物、抑制剂和调节剂联合测定。这两种酶有19%的序列相同，二级结构彼此相似。这些酶的不同之处在于它们对金属离子的使用和反馈抑制的调节。因此，这些研究的最终目的是确定这些酶之间的相似性和可能的同源性。这些酶分别催化磷酸烯醇丙酮酸与含有四个（4-磷酸红）和五个（5-磷酸阿拉伯糖）碳的糖分子的缩合。在这两种情况下，都发生了不寻常的劈裂，即磷酸烯醇丙酮酸的碳-氧键被劈裂，而氧-磷键没有。这两种酶在革兰氏阴性菌的生物合成途径中都处于重要的位置，一个导致芳香终产物，另一个导致革兰氏阴性菌外膜的脂多糖。本次x射线晶体学结构研究的总体目标是了解这两种酶在底物结合和作用机制上的异同，以及这两种酶是同源物还是通过趋同进化产生的。＊＊＊