PDBsum entry: 1hti

Isomerase(intramolecular oxidoreductase)

PDB id: 1hti

Contents

Protein chains

248 a.a. *

Ligands

PGA

* Residue conservation analysis

PDB id:

1hti

Name:

Isomerase(intramolecular oxidoreductase)

Title:

Crystal structure of recombinant human triosephosphate isomerase at 2.8 angstroms resolution. Triosephosphate isomerase related human genetic disorders and comparison with the trypanosomal enzyme

Structure:

Triosephosphate isomerase. Chain: a, b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606

Biol. unit:

Dimer (from PQS)

Resolution:

2.80Å R-factor: 0.167

Authors:

S.C.Mande,W.G.J.Hol

Key ref:

S.C.Mande et al. (1994). Crystal structure of recombinant human triosephosphate isomerase at 2.8 A resolution. Triosephosphate isomerase-related human genetic disorders and comparison with the trypanosomal enzyme. Protein Sci, 3, 810-821. PubMed id: 8061610 Ref: Full text

Date:

12-Oct-94 Release date: 26-Jan-95

Protein chains

P60174  (TPIS_HUMAN) -  Triosephosphate isomerase

Seq: 249 a.a.

Struc: 248 a.a.

Enzyme reactions

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

D-glyceraldehyde 3-phosphate (Bound ligand (Het Group name = PGA) matches with 72.00% similarity) = glycerone phosphate

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

 Gene Ontology (GO) functional annotation 

• Cellular component: soluble fraction (3 terms)
• Biological process: metabolic process (11 terms)
• Biochemical function: catalytic activity (4 terms)

Added reference

Full text	Protein Sci 3:810-821 (1994)
PubMed id: 8061610

Crystal structure of recombinant human triosephosphate isomerase at 2.8 A resolution. Triosephosphate isomerase-related human genetic disorders and comparison with the trypanosomal enzyme.

S.C.Mande, V.Mainfroid, K.H.Kalk, K.Goraj, J.A.Martial, W.G.Hol.

ABSTRACT

The crystal structure of recombinant human triosephosphate isomerase (hTIM) has been determined complexed with the transition-state analogue 2-phosphoglycolate at a resolution of 2.8 A. After refinement, the R-factor is 16.7% with good geometry. The asymmetric unit contains 1 complete dimer of 53,000 Da, with only 1 of the subunits binding the inhibitor. The so-called flexible loop, comprising residues 168-174, is in its "closed" conformation in the subunit that binds the inhibitor, and in the "open" conformation in the other subunit. The tips of the loop in these 2 conformations differ up to 7 A in position. The RMS difference between hTIM and the enzyme of Trypanosoma brucei, the causative agent of sleeping sickness, is 1.12 A for 487 C alpha positions with 53% sequence identity. Significant sequence differences between the human and parasite enzymes occur at about 13 A from the phosphate binding site. The chicken and human enzymes have an RMS difference of 0.69 A for 484 equivalent residues and about 90% sequence identity. Complementary mutations ensure a great similarity in the packing of side chains in the core of the beta-barrels of these 2 enzymes. Three point mutations in hTIM have been correlated with severe genetic disorders ranging from hemolytic disorder to neuromuscular impairment. Knowledge of the structure of the human enzyme provides insight into the probable effect of 2 of these mutations, Glu 104 to Asp and Phe 240 to Ile, on the enzyme. The third mutation reported to be responsible for a genetic disorder, Gly 122 to Arg, is however difficult to explain. This residue is far away from both catalytic centers in the dimer, as well as from the dimer interface, and seems unlikely to affect stability or activity. Inspection of the 3-dimensional structure of trypanosomal triosephosphate isomerase, which has a methionine at position 122, only increased the mystery of the effects of the Gly to Arg mutation in the human enzyme.

Selected figure(s)

Figure 5.
Fig. 5. Interactionsof -PC withhTIM. The 3,,,-helix,compisingresidues533- 537, points directly n the phosphate moiety. Also hown is the unusual phosphate-carbonyl (Gly 510) interac- tion. This figure was produced using MOLSCRIPT.

Figure 8.
Fig. 8.Mutation of phenylalanine to at position 240 resulting in genetic disorder in hTIM (Chang et 993). The and the 2-PG molecule are shown in ball-and-stick representations. The orientation is cho- sensuch thatthe 310-helixisseen point- ing toward the phosphate. The adjoining &strand is shown terminating in the cat- alytic Lys313.

The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1994, 3, 810-821) copyright 1994.

Figures were selected by an automated process.