4ZVJ

Structure of human triose phosphate isomerase K13M

4ZVJ の概要

• エントリーDOI: 10.2210/pdb4zvj/pdb
• 分子名称: Triosephosphate isomerase, SODIUM ION, POTASSIUM ION, ... (4 entities in total)
• 機能のキーワード: triose phosphate isomerase, tim, dimer, glycolysis, isomerase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 54518.15

構造登録者

Amrich, C.G.,Smith, C.,Heroux, A.,VanDemark, A.P. (登録日: 2015-05-18, 公開日: 2016-03-09, 最終更新日: 2023-09-27)

主引用文献

Roland, B.P.,Amrich, C.G.,Kammerer, C.J.,Stuchul, K.A.,Larsen, S.B.,Rode, S.,Aslam, A.A.,Heroux, A.,Wetzel, R.,VanDemark, A.P.,Palladino, M.J.
Triosephosphate isomerase I170V alters catalytic site, enhances stability and induces pathology in a Drosophila model of TPI deficiency.
Biochim. Biophys. Acta, 1852:61-69, 2015

PubMed Abstract: Triosephosphate isomerase (TPI) is a glycolytic enzyme which homodimerizes for full catalytic activity. Mutations of the TPI gene elicit a disease known as TPI Deficiency, a glycolytic enzymopathy noted for its unique severity of neurological symptoms. Evidence suggests that TPI Deficiency pathogenesis may be due to conformational changes of the protein, likely affecting dimerization and protein stability. In this report, we genetically and physically characterize a human disease-associated TPI mutation caused by an I170V substitution. Human TPI(I170V) elicits behavioral abnormalities in Drosophila. An examination of hTPI(I170V) enzyme kinetics revealed this substitution reduced catalytic turnover, while assessments of thermal stability demonstrated an increase in enzyme stability. The crystal structure of the homodimeric I170V mutant reveals changes in the geometry of critical residues within the catalytic pocket. Collectively these data reveal new observations of the structural and kinetic determinants of TPI Deficiency pathology, providing new insights into disease pathogenesis.

PubMed: 25463631
DOI: 10.1016/j.bbadis.2014.10.010

実験手法

X-RAY DIFFRACTION (1.6996 Å)