PDBsum entry: 1m6j

Isomerase

PDB id: 1m6j

Contents

Protein chains

260 a.a. *

Waters ×783

* Residue conservation analysis

PDB id:

1m6j

Name:

Isomerase

Title:

Crystal structure of triosephosphate isomerase from entamoeba histolytica

Structure:

Triosephosphate isomerase. Chain: a, b. Synonym: tim, tpi. Engineered: yes

Source:

Entamoeba histolytica. Organism_taxid: 5759. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

1.50Å R-factor: 0.184 R-free: 0.206

Authors:

A.Rodriguez-Romero,A.Hernandez-Santoyo,D.A.Fernandez-Velasco

Key ref:

A.Rodríguez-Romero et al. (2002). Structure and inactivation of triosephosphate isomerase from Entamoeba histolytica. J Mol Biol, 322, 669-675. PubMed id: 12270704 DOI: 10.1016/S0022-2836(02)00809-4

Date:

16-Jul-02 Release date: 12-Oct-02

Protein chains

O02611  (TPIS_ENTHI) -  Triosephosphate isomerase

Seq: 261 a.a.

Struc: 260 a.a.

Enzyme reactions

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

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

 Gene Ontology (GO) functional annotation 

• Biological process: metabolic process (6 terms)
• Biochemical function: catalytic activity (3 terms)

Added reference

DOI no: 10.1016/S0022-2836(02)00809-4

J Mol Biol 322:669-675 (2002)

PubMed id: 12270704

Structure and inactivation of triosephosphate isomerase from Entamoeba histolytica.

A.Rodríguez-Romero, A.Hernández-Santoyo, L.del Pozo Yauner, A.Kornhauser, D.A.Fernández-Velasco.

ABSTRACT

Triosephosphate isomerase (TIM) has been proposed as a target for drug design. TIMs from several parasites have a cysteine residue at the dimer interface, whose derivatization with thiol-specific reagents induces enzyme inactivation and aggregation. TIMs lacking this residue, such as human TIM, are less affected. TIM from Entamoeba histolytica (EhTIM) has the interface cysteine residue and presents more than ten insertions when compared with the enzyme from other pathogens. To gain further insight into the role that interface residues play in the stability and reactivity of these enzymes, we determined the high-resolution structure and characterized the effect of methylmethane thiosulfonate (MMTS) on the activity and conformational properties of EhTIM. The structure of this enzyme was determined at 1.5A resolution using molecular replacement, observing that the dimer is not symmetric. EhTIM is completely inactivated by MMTS, and dissociated into stable monomers that possess considerable secondary structure. Structural and spectroscopic analysis of EhTIM and comparison with TIMs from other pathogens reveal that conformational rearrangements of the interface after dissociation, as well as intramonomeric contacts formed by the inserted residues, may contribute to the unusual stability of the derivatized EhTIM monomer.

Selected figure(s)

Figure 2.
Figure 2. The 2F[o] -F[c] density maps. Stereo view of the interface Cys14 surrounded by residues of the facing subunit (loop 3). Cys14 SgH (monomer B) and His86 Nd1 (monomer A) are at hydrogen bond distance (top panel). The water network at the surface of the enzyme near Lys129 and Pro96 showing ringed water structure (bottom panel). The maps are contoured at the 1s level.

Figure 3.
Figure 3. Structural comparison of triosephosphate isomerases. (a) C^a superposition of EhTIM (green), TbTIM (blue) and TcTIM (orange). Two insertions of the EhTIM structure are indicated (residues 36-38 and 59-62). (b) C^a superposition of monomers A (green) and B (blue) in EhTIM, differences at loop 3 and 6 are evident. These Figures were created with GRASP.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 322, 669-675) copyright 2002.

Figures were selected by an automated process.