PDBsum entry: 1n1g

Oxidoreductase

PDB id: 1n1g

Contents

Protein chain

346 a.a. *

Ligands

BCP ×3

PLM

Waters ×81

* Residue conservation analysis

PDB id:

1n1g

Name:

Oxidoreductase

Title:

Crystal structure of leishmania mexicana glycerol-3-phosphat dehydrogenase with inhibitor bcp

Structure:

Glycerol-3-phosphate dehydrogenase. Chain: a. Engineered: yes

Source:

Leishmania mexicana. Organism_taxid: 5665. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.50Å R-factor: 0.207 R-free: 0.231

Authors:

J.Choe,W.G.Hol

Key ref:

J.Choe et al. (2002). Anomalous differences of light elements in determining precise binding modes of ligands to glycerol-3-phosphate dehydrogenase. Chem Biol, 9, 1189-1197. PubMed id: 12445769 DOI: 10.1016/S1074-5521(02)00243-0

Date:

17-Oct-02 Release date: 28-Oct-03

Protein chain

P90551  (GPDA_LEIME) -  Glycerol-3-phosphate dehydrogenase [NAD+], glycosomal

Seq: 366 a.a.

Struc: 346 a.a.

Enzyme reactions

• Enzyme class: E.C.1.1.1.8 - Glycerol-3-phosphate dehydrogenase (NAD(+)).
• Reaction: sn-glycerol 3-phosphate + NAD⁺ = glycerone phosphate + NADH

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

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (4 terms)
• Biological process: oxidation-reduction process (4 terms)
• Biochemical function: nucleotide binding (7 terms)

reference

DOI no: 10.1016/S1074-5521(02)00243-0

Chem Biol 9:1189-1197 (2002)

PubMed id: 12445769

Anomalous differences of light elements in determining precise binding modes of ligands to glycerol-3-phosphate dehydrogenase.

J.Choe, S.Suresh, G.Wisedchaisri, K.J.Kennedy, M.H.Gelb, W.G.Hol.

ABSTRACT

Pathogenic protozoa such as Trypanosome and Leishmania species cause tremendous suffering worldwide. Because of their dependence on glycolysis for energy, the glycolytic enzymes of these organisms, including glycerol-3-phosphate dehydrogenase (GPDH), are considered attractive drug targets. Using the adenine part of NAD as a lead compound, several 2,6-disubstituted purines were synthesized as inhibitors of Leishmania mexicana GPDH (LmGPDH). The electron densities for the inhibitor 2-bromo-6-chloro-purine bound to LmGPDH using a "conventional" wavelength around 1 A displayed a quasisymmetric shape. The anomalous signals from data collected at 1.77 A clearly indicated the positions of the halogen atoms and revealed the multiple binding modes of this inhibitor. Intriguing differences in the observed binding modes of the inhibitor between very similarly prepared crystals illustrate the possibility of crystal-to-crystal variations in protein-ligand complex structures.

Selected figure(s)

Figure 2.
Figure 2. Electron Densities of the Bound Inhibitor BCP(A) Model-unbiased, sigmaA-weighted Fo-Fc map contoured at 3 σ (light brown), 5 σ (violet), and 7 σ (red) with conformation A of BCP.(B and C) Two alternative conformations (conformation A, green; conformation B, red) of BCP bound to L. mexicana GPDH in a model-unbiased, sigmaA-weighted Fo-Fc map (B) contoured at 3.5 σ (light brown) and an anomalous difference Fourier map contoured at 4.5 σ (red) and (C) an anomalous difference Fourier map contoured at 5.5 σ (red). Carbon, nitrogen, chlorine, and bromine are colored brown, blue, yellow, and pink, respectively. Drawn using MOLSCRIPT [45] and Raster3D [46].

Figure 4.
Figure 4. Electron Densities for the Bound Inhibitor BOP(A) Model-unbiased, sigmaA-weighted Fo-Fc map of BOP bound to LmGPDH contoured at 2.4 σ (pink) and the anomalous difference Fourier map (red) contoured at 10 σ superimposed with the final model of BOP.(B) The anomalous difference Fourier map (red) contoured at 10 σ for the whole protein region drawn with the C^α model of the LmGPDH and inhibitor BOP. Carbon, nitrogen, oxygen, and bromine are colored brown, blue, red, and pink, respectively.

The above figures are reprinted by permission from Cell Press: Chem Biol (2002, 9, 1189-1197) copyright 2002.

Figures were selected by an automated process.