PDBsum entry 4poc

Isomerase

PDB id: 4poc

Contents

Protein chains

246 a.a.

Ligands

PO4

Metals

_BR ×2

__K ×2

_NA

Waters ×327

PDB id:

4poc

Name:

Isomerase

Title:

Structure of triosephosphate isomerase wild type human enzyme.

Structure:

Triosephosphate isomerase. Chain: a, b. Synonym: tim, triose-phosphate isomerase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tpi, tpi1. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.60Å R-factor: 0.155 R-free: 0.187

Authors:

C.G.Amrich,A.A.Aslam,A.Heroux,A.P.Vandemark

Key ref:

B.P.Roland et al. (2015). Triosephosphate isomerase I170V alters catalytic site, enhances stability and induces pathology in a Drosophila model of TPI deficiency. Biochim Biophys Acta, 1852, 61-69. PubMed id: 25463631 DOI: 10.1016/j.bbadis.2014.10.010

Date:

25-Feb-14 Release date: 14-Jan-15

Protein chains

P60174  (TPIS_HUMAN) -  Triosephosphate isomerase from Homo sapiens

Seq: 249 a.a.

Struc: 246 a.a.

Enzyme reactions

• Enzyme class 2: E.C.4.2.3.3 - methylglyoxal synthase.
• Reaction: dihydroxyacetone phosphate = methylglyoxal + phosphate

dihydroxyacetone phosphate = methylglyoxal + phosphate (Bound ligand (Het Group name = PO4) corresponds exactly)

• Enzyme class 3: E.C.5.3.1.1 - triose-phosphate isomerase.
• Reaction: D-glyceraldehyde 3-phosphate = dihydroxyacetone phosphate

D-glyceraldehyde 3-phosphate (Bound ligand (Het Group name = PO4) matches with 50.00% similarity) = dihydroxyacetone phosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.bbadis.2014.10.010

Biochim Biophys Acta 1852:61-69 (2015)

PubMed id: 25463631

Triosephosphate isomerase I170V alters catalytic site, enhances stability and induces pathology in a Drosophila model of TPI deficiency.

B.P.Roland, C.G.Amrich, C.J.Kammerer, K.A.Stuchul, S.B.Larsen, S.Rode, A.A.Aslam, A.Heroux, R.Wetzel, A.P.VanDemark, M.J.Palladino.

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.