PDBsum entry: 2pu1

Lyase

PDB-id: 2pu1

Contents

Description

Header details

Header records

References

PROCHECK

Protein chain

431 a.a. *

Ligands

FSG

EDO

Metal ions

_ZN ×3

Waters ×354

* Residue conservation analysis

Tools

Clefts Calculation

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.

UniProt:

Q9NDH8 (Q9NDH8_TRYBB)

Seq:

Struc:

Seq:

429 a.a.

Struc:

431 a.a.*

Key:

PfamA domain

Secondary structure

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

Enzyme class:

E.C.4.2.1.11   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:

2-phospho-D-glycerate = phosphoenolpyruvate + H₂O (see diagram below)

Cofactor:

Magnesium

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

Related entries:

1oep
first structure of the t. Brucei enolase
2ptw
the same protein complexed with sulphate and zn ion in a
metal binding site iv
2ptx
closed conformation of the t. Brucei enolase complexed with
sulphate
2pty
the same protein complexed with pep
... plus others (see Header records)

Quick_links

Procheck

Clefts

Surface

Key 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.