Modulation of the Heme Pocket Conformation or Dual Concerted Mechanism upon Substitution of Hydrogen Sulfide by Oxygen Binding to an Unusual Hemoglobin?

通过与异常血红蛋白结合的氧取代硫化氢来调节血红素口袋构象或双重协同机制？

• 批准号: 9974961
• 负责人: Juan Lopez-Garriga
• 金额: $ 24万
• 依托单位: University of Puerto Rico Mayaguez
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9974961&HistoricalAwards=false
• 关键词: Modulation; Heme; Pocket; Conformation; Dual

Lopez-GarrigaMCB-9974961The objective of this research is to investigate the molecular basis for oxidation-reduction, ligand selection, and ligand stabilization processes of hemoglobin (HbI) isolated from Lucina pectinata. This hemoglobin is probably the only heme protein that carries out its function, to transport H2S to a bacteria symbion, in a hydrogen-sulfide bound ferric state. The presence of H-bonding between the heme-Fe+3 SH2 moiety and the Gln(E7) group is postulated to stabilize the HbISH2 center. Likewise, other amino groups, in particular, Gln(E7), Phe(B10), and Phe(E11) may interact with other HbI ligands, CO and O2. In order to understand the structural and functional characteristics of this enzyme, site-directed mutants of HbI will be used to determine its association and dissociation constants with different ligands as a function of pH. These studies in conjunction with the FTIR and resonance Raman work should produce new insight about factors that control H2S binding, transport, and delivery. The goal of this research is to study the ligand affinity differences in heme proteins. At present, it is not established whether these differences arise from electrostatic effects, from steric constraints, or from hydrogen-bonding differences. It is hoped that the these studies with hemoglobin I from Lucina pectinata will resolve some of these issues and produce new insight about the structural and functional characteristics of this unusual hemoglobin. The work is likely to produce information that may be useful in the design of recombinant HbI proteins with commercial uses, for example, as a specific H2S biosensor. These proteins may also be used for the removal of toxic H2S from industrial or natural processes, such as anaerobic fermentation, sewage, and natural gas production.

Lopez-GarrigaMCB-9974961本研究的目的是研究从 Lucina pectinata 中分离的血红蛋白 (HbI) 的氧化还原、配体选择和配体稳定过程的分子基础。 这种血红蛋白可能是唯一发挥其功能的血红素蛋白，以硫化氢结合的铁态将 H2S 转运至细菌共生体。 假定血红素-Fe+3 SH2 部分和 Gln(E7) 基团之间存在氢键以稳定 HbISH2 中心。 同样，其他氨基，特别是 Gln(E7)、Phe(B10) 和 Phe(E11) 可能与其他 HbI 配体、CO 和 O2 相互作用。 为了了解该酶的结构和功能特征，将使用 HbI 的定点突变体来确定其与不同配体的缔合和解离常数随 pH 的变化。 这些研究与 FTIR 和共振拉曼工作相结合，应该会对控制 H2S 结合、运输和传递的因素产生新的见解。本研究的目的是研究血红素蛋白的配体亲和力差异。 目前，尚不清楚这些差异是由静电效应、空间限制还是氢键差异引起的。 希望这些针对来自 Lucina pectinata 的血红蛋白 I 的研究能够解决其中一些问题，并对这种不寻常的血红蛋白的结构和功能特征产生新的见解。 这项工作可能会产生可用于设计具有商业用途的重组 HbI 蛋白的信息，例如作为特定的 H2S 生物传感器。 这些蛋白质还可用于去除工业或自然过程中的有毒 H2S，例如厌氧发酵、污水和天然气生产。