PDBsum entry 4z0s

Isomerase

PDB id: 4z0s

Contents

Protein chains

247 a.a.

Ligands

EDO ×7

Waters ×81

PDB id:

4z0s

Name:

Isomerase

Title:

F96a mutant of plasmodium falciparum triosephosphate isomerase

Structure:

Triosephosphate isomerase. Chain: a, b. Synonym: tim,triose-phosphate isomerase. Engineered: yes. Mutation: yes. Other_details: mutation of a163v present in the wild type tim considered as template

Source:

Plasmodium falciparum. Organism_taxid: 5833. Gene: tpi. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.39Å R-factor: 0.230 R-free: 0.271

Authors:

V.Pareek,P.Balaram,M.R.N.Murthy

Key ref:

V.Pareek et al. (2016). Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate Isomerase: Insights from a Rare Variation at Residue 96 in the Plasmodial Enzyme. Chembiochem, 17, 620-629. PubMed id: 26762569 DOI: 10.1002/cbic.201500532

Date:

26-Mar-15 Release date: 03-Feb-16

Protein chains

Q07412  (TPIS_PLAFA) -  Triosephosphate isomerase from Plasmodium falciparum

Seq: 248 a.a.

Struc: 247 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: 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 = EDO) matches with 40.00% similarity) = dihydroxyacetone phosphate

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

Added reference

DOI no: 10.1002/cbic.201500532

Chembiochem 17:620-629 (2016)

PubMed id: 26762569

Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate Isomerase: Insights from a Rare Variation at Residue 96 in the Plasmodial Enzyme.

V.Pareek, M.Samanta, N.V.Joshi, H.Balaram, M.R.Murthy, P.Balaram.

ABSTRACT

Despite extensive research into triosephosphate isomerases (TIMs), there exists a gap in understanding of the remarkable conjunction between catalytic loop-6 (residues 166-176) movement and the conformational flip of Glu165 (catalytic base) upon substrate binding that primes the active site for efficient catalysis. The overwhelming occurrence of serine at position 96 (98 % of the 6277 unique TIM sequences), spatially proximal to E165 and the loop-6 residues, raises questions about its role in catalysis. Notably, Plasmodium falciparum TIM has an extremely rare residue-phenylalanine-at this position whereas, curiously, the mutant F96S was catalytically defective. We have obtained insights into the influence of residue 96 on the loop-6 conformational flip and E165 positioning by combining kinetic and structural studies on the PfTIM F96 mutants F96Y, F96A, F96S/S73A, and F96S/L167V with sequence conservation analysis and comparative analysis of the available apo and holo structures of the enzyme from diverse organisms.