PDBsum entry 1vga

Isomerase

PDB id: 1vga

Contents

Protein chains

246 a.a. *

Waters ×558

* Residue conservation analysis

PDB id:

1vga

Name:

Isomerase

Title:

Structures of unligated and inhibitor complexes of w168f mutant of triosephosphate isomerase from plasmodium falciparum

Structure:

Triosephosphate isomerase. Chain: a, b, c, d. Synonym: tim. Engineered: yes. Mutation: yes

Source:

Plasmodium falciparum. Malaria parasite p. Falciparum. Organism_taxid: 5833. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Dimer (from PQS)

Resolution:

1.80Å R-factor: 0.207 R-free: 0.229

Authors:

K.Eaazhisai,H.Balaram,P.Balaram,M.R.N.Murthy

Key ref:

K.Eaazhisai et al. (2004). Structures of unliganded and inhibitor complexes of W168F, a Loop6 hinge mutant of Plasmodium falciparum triosephosphate isomerase: observation of an intermediate position of loop6. J Mol Biol, 343, 671-684. PubMed id: 15465054 DOI: 10.1016/j.jmb.2004.08.060

Date:

23-Apr-04 Release date: 26-Oct-04

Protein chains

Q07412  (TPIS_PLAFA) -  Triosephosphate isomerase from Plasmodium falciparum

Seq: 248 a.a.

Struc: 246 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

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

Added reference

DOI no: 10.1016/j.jmb.2004.08.060

J Mol Biol 343:671-684 (2004)

PubMed id: 15465054

Structures of unliganded and inhibitor complexes of W168F, a Loop6 hinge mutant of Plasmodium falciparum triosephosphate isomerase: observation of an intermediate position of loop6.

K.Eaazhisai, H.Balaram, P.Balaram, M.R.Murthy.

ABSTRACT

The enzymatic reaction of triosephosphate isomerase (TIM) is controlled by the movement of a loop (loop6, residues 166-176). Crystal structures of TIMs from a variety of sources have revealed that the loop6, which is in an open conformation in the unliganded enzyme, adopts a closed conformation in inhibitor complexes. In contrast, structures with loop open conformation are obtained in most of the complexes of TIM from the malarial parasite Plasmodium falciparum (PfTIM). W168 is a conserved N-terminal hinge residue, involved in different sets of interactions in the "open" and "closed" forms of loop6. The role of W168 in determining the loop conformation was examined by structural studies on the mutant W168F and its complexes with ligands. The three-dimensional structures of unliganded mutant (1.8 A) and complexes with sulfate (2.8 A) and glycerol-2-phosphate (G2P) (2.8 A) have been determined. Loop6 was found disordered in these structures, reflecting the importance of W168 in stabilizing either the open or the closed states. Critical sequence differences between the Plasmodium enzyme and other TIMs may influence the equilibrium between the closed and open forms. Examination of the environment of the loop6 shows that its propensity for the open or the closed forms is influenced not only by Phe96 as suggested earlier, but also by Asn233, which occurs in the vicinity of the active site. This residue is Gly in the other TIM sequences and probably plays a crucial role in the mode of ligand binding, which in turn affects the loop opening/closing process in PfTIM.

Selected figure(s)

Figure 1.
Figure 1. (a) Ribbon representation of the structure of PfTIM monomer. Trp11 (blue) and Trp168 (green) are shown in sticks. (b) and (c) Hydrogen bonding interactions of the N-terminal hinge residues, Pro166, Leu167 and Trp168 in the open and closed forms of loop6, respectively. The Figures were generated using MOLSCRIPT39 and rendered using Raster3D.40 (d) Chemical structures of the substrates and various ligands of TIM; dihydroxyacetone phosphate (DHAP), glyceraldehyde-3-phosphate (GAP), 2-phosphoglycolate (PGA), 2-phosphoglycerate (2PG), glycerol-3-phosphate (G-3P) and glycerol-2-phosphate (G-2P).

Figure 3.
Figure 3. Stereo view of the ligand binding site in the structures of W168F mutant of PfTIM complexed with sulfate and G2P. (a) Fit of the sulfate ion to the electron density in a F[obs] -F[calc] omit map contoured at 2.5s. (b) Superposition of the active sites of sulfate complexes of TrypTIM (green), C. elegans TIM (indigo) and W168F mutant of PfTIM (colored by atom) showing the differences in the protein-ligand interactions. (c) G2P at the active site of the B-subunit of W168F-G2P complex is shown with density from the F[obs] -F[calc] omit map contoured at 2.5s. (d) Hydrogen bonding interactions (dotted lines) of G2P with the polypeptide.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 343, 671-684) copyright 2004.

Figures were selected by an automated process.