4ZVJ: Structure of human triose phosphate isomerase K13M

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.
PDB ID: 4ZVJDownload
MMDB ID: 137211
PDB Deposition Date: 2015/5/18
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 1.6996  Å
Source Organism:
Similar Structures:
Biological Unit for 4ZVJ: dimeric; determined by author and by software (PISA)
Molecular Components in 4ZVJ
Label Count Molecule
Proteins (2 molecules)
Triosephosphate Isomerase(Gene symbol: TPI1)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

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