课题基金 / 基金详情

METABOLIC SPECIFICITY OF METHYLTHIOCOFORMYCIN FOR MALARIAL ADENOSINE DEAMINASE

METABOLIC SPECIFICITY OF METHYLTHIOCOFORMYCIN FOR MALARIAL ADENOSINE DEAMINASE
甲硫基辅霉素对疟疾腺苷脱氨酶的代谢特异性
批准号:
8169275
负责人:
STEVEN G ALMO
金额:
$0.17万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-04-01 至 2011-03-31

项目摘要

项目成果

STEVEN G ALMO的其他基金

相似基金

相关文献

中文摘要
翻译
这个子项目是众多研究子项目之一
英文摘要
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. Plasmodium falciparum is a purine auxotroph requiring hypoxanthine as a key metabolic precursor. Erythrocyte adenine nucleotides are the source of the purine precursors, making adenosine deaminase (ADA) a key enzyme in the pathway of hypoxanthine formation in Plasmodium falciparum. Methylthioadenosine (MTA) is one of purine nucleotide substrates for most malarial ADAs, but not for human ADA. The catalytic site specificity of malarial ADAs permits methylthiocoformycin (MT-coformycin) to act as a Plasmodium-specific transition state analogue with low affinity for human ADA [Tyler, P. C., Taylor, E. A., Frohlich, R. G. G., and Schramm, V. L. (2007) J. Am. Chem. Soc. 129, 6872-6879]. The structural basis for MTA and MT-coformycin specificity in malarial ADAs is the subject of speculation. In this study, we report the crystal structure of ADA from Plasmodium vivax (PvADA) in a complex with MT-coformycin that reveals an unprecedented binding geometry for 5'-methylthioribosyl groups in the malarial ADAs. Compared to malarial ADA complexes with adenosine or deoxycoformycin, 5'-methylthioribosyl groups are rotated 130 degrees . A hydrogen bonding network between Asp172 and the 3'-hydroxyl of MT-coformycin is essential for recognition of the 5'-methylthioribosyl group. Water occupies the 5'-hydroxyl binding site when MT-coformycin is bound. Mutagenesis of Asp172 destroys the substrate specificity for MTA and MT-coformycin. Kinetic, mutagenic, and structural analyses of PvADA and kinetic analysis of five other Plasmodium ADAs establish the unique structural basis for its specificity for MTA and MT-coformycin. Plasmodium gallinaceum ADA does not use MTA as a substrate, is not inhibited by MT-coformycin, and is missing Asp172.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
CRYSTAL STRUCTURE OF DCR3-TL1A COMPLEX
  • 批准号:
    8169276
  • 项目类别:
  • 资助金额:
    $0.18万
  • 财政年份:
    2010
  • 负责人:
    STEVEN G ALMO
  • 依托单位:
CRYSTAL STRUCTURE OF DCR3-TL1A COMPLEX
  • 批准号:
    7955210
  • 项目类别:
  • 资助金额:
    $0.53万
  • 财政年份:
    2009
  • 负责人:
    STEVEN G ALMO
  • 依托单位:
MALARIAL ADENOSINE DEAMINASES
  • 批准号:
    7955209
  • 项目类别:
  • 资助金额:
    $0.54万
  • 财政年份:
    2009
  • 负责人:
    STEVEN G ALMO
  • 依托单位:
国内基金
海外基金
基于ADK/Adenosine调控DNA甲基化探讨“利湿化瘀通络”法对2型糖尿病肾病足细胞裂孔膜损伤的干预机制研究
  • 批准号:
    82074359
  • 项目类别:
    面上项目
  • 资助金额:
    55.0万元
  • 批准年份:
    2020
  • 负责人:
    安晓飞
  • 依托单位:
细胞外腺苷(Adenosine)作为干细胞旁分泌因子的生物学鉴定和功能分析
Adenosine诱导A1/A2AR稳态失衡启动慢性低灌注白质炎性损伤及其机制