PDBsum entry: 2pu1

Lyase

PDB id: 2pu1

Contents

Protein chain

431 a.a. *

Ligands

FSG

EDO

Metals

_ZN ×3

Waters ×354

* Residue conservation analysis

PDB id:

2pu1

Name:

Lyase

Title:

Crystal structure of the t. Brucei enolase complexed with fluoro-phosphonoacetohydroxamate (fpah)

Structure:

Enolase. Chain: a. Synonym: 2-phospho-d-glycerate hydro-lyase. Engineered: yes. Mutation: yes

Source:

Trypanosoma brucei. Organism_taxid: 5691. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.80Å R-factor: 0.165 R-free: 0.206

Authors:

M.V.A.S.Navarro,D.J.Rigden,R.C.Garratt,S.M.G.Dias

Key ref:

M.V.Navarro et al. (2007). Structural flexibility in Trypanosoma brucei enolase revealed by X-ray crystallography and molecular dynamics. Febs J, 274, 5077-5089. PubMed id: 17822439 DOI: 10.1111/j.1742-4658.2007.06027.x

Date:

08-May-07 Release date: 20-Nov-07

Protein chain

Q9NDH8  (Q9NDH8_TRYBB) -  Enolase

Seq: 429 a.a.

Struc: 431 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.4.2.1.11 - Phosphopyruvate hydratase.
• Reaction: 2-phospho-D-glycerate = phosphoenolpyruvate + H₂O

2-phospho-D-glycerate = phosphoenolpyruvate (Bound ligand (Het Group name = EDO) matches with 40.00% similarity) + H(2)O

• Cofactor: Magnesium

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

 Gene Ontology (GO) functional annotation 

• Cellular component: cell surface (3 terms)
• Biological process: glycolysis (1 term)
• Biochemical function: lyase activity (3 terms)

Added reference

DOI no: 10.1111/j.1742-4658.2007.06027.x

Febs J 274:5077-5089 (2007)

PubMed id: 17822439

Structural flexibility in Trypanosoma brucei enolase revealed by X-ray crystallography and molecular dynamics.

M.V.Navarro, S.M.Gomes Dias, L.V.Mello, M.T.da Silva Giotto, S.Gavalda, C.Blonski, R.C.Garratt, D.J.Rigden.

ABSTRACT

Enolase is a validated drug target in Trypanosoma brucei. To better characterize its properties and guide drug design efforts, we have determined six new crystal structures of the enzyme, in various ligation states and conformations, and have carried out complementary molecular dynamics simulations. The results show a striking structural diversity of loops near the catalytic site, for which variation can be interpreted as distinct modes of conformational variability that are explored during the molecular dynamics simulations. Our results show that sulfate may, unexpectedly, induce full closure of catalytic site loops whereas, conversely, binding of inhibitor phosphonoacetohydroxamate may leave open a tunnel from the catalytic site to protein surface offering possibilities for drug development. We also present the first complex of enolase with a novel inhibitor 2-fluoro-2-phosphonoacetohydroxamate. The molecular dynamics results further encourage efforts to design irreversible species-specific inhibitors: they reveal that a parasite enzyme-specific lysine may approach the catalytic site more closely than crystal structures suggest and also cast light on the issue of accessibility of parasite enzyme-specific cysteines to chemically modifying reagents. One of the new sulfate structures contains a novel metal-binding site IV within the catalytic site cleft.