1NJJ

Crystal structure determination of T. brucei ornithine decarboxylase bound to D-ornithine and to G418

PDB DOI: https://doi.org/10.2210/pdb1NJJ/pdb

Classification: LYASE
Organism(s): Trypanosoma brucei gambiense
Expression System: Escherichia coli BL21
Mutation(s): No

Deposited: 2002-12-31 Released: 2003-08-26
Deposition Author(s): Jackson, L.K., Goldsmith, E.J., Phillips, M.A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.45 Å
R-Value Free: 0.283
R-Value Work: 0.260

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.4 of the entry. See complete history.

Literature

X-ray Structure Determination of Trypanosoma brucei Ornithine Decarboxylase Bound to D-Ornithine and to G418: INSIGHTS INTO SUBSTRATE BINDING AND ODC CONFORMATIONAL FLEXIBILITY.

Jackson, L.K., Goldsmith, E.J., Phillips, M.A.

(2003) J Biol Chem 278: 22037-22043

PubMed: 12672797 Search on PubMed
DOI: https://doi.org/10.1074/jbc.M300188200
Primary Citation of Related Structures:
1NJJ

PubMed Abstract:
Ornithine decarboxylase (ODC) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the rate-determining step in the biosynthesis of polyamines. ODC is a proven drug target to treat African sleeping sickness. The x-ray crystal structure of Trypanosoma brucei ODC in complex with d-ornithine (d-Orn), a substrate analog, and G418 (Geneticin), a weak non-competitive inhibitor, was determined to 2.5-A resolution. d-Orn forms a Schiff base with PLP, and the side chain is in a similar position to that observed for putrescine and alpha-difluoromethylornithine in previous T. brucei ODC structures. The d-Orn carboxylate is positioned on the solvent-exposed side of the active site (si face of PLP), and Gly-199, Gly-362, and His-197 are the only residues within 4.2 A of this moiety. This structure confirms predictions that the carboxylate of d-Orn binds on the si face of PLP, and it supports a model in which the carboxyl group of the substrate l-Orn would be buried on the re face of the cofactor in a pocket that includes Phe-397, Tyr-389, Lys-69 (methylene carbons), and Asp-361. Electron density for G418 was observed at the boundary between the two domains within each ODC monomer. A ten-amino acid loop region (392-401) near the 2-fold axis of the dimer interface, which contributes several residues that form the active site, is disordered in this structure. The disordering of residues in the active site provides a potential mechanism for inhibition by G418 and suggests that allosteric inhibition from this site is feasible.

Organizational Affiliation

Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, 5323 Harry Hines Boulevard, TX 75390-9041, USA.

Macromolecule Content

Total Structure Weight: 191.55 kDa
Atom Count: 11,424
Modelled Residue Count: 1,404
Deposited Residue Count: 1,700
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
ornithine decarboxylase	A, B, C, D	425	Trypanosoma brucei gambiense	Mutation(s): 0 EC: 4.1.1.17
UniProt
Find proteins for Q9TZZ6 (Trypanosoma brucei gambiense) Explore Q9TZZ6 Go to UniProtKB: Q9TZZ6
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9TZZ6
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
GET Query on GET Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain G [auth B] SDF format, chain I [auth C] MOL2 format, chain E [auth A] MOL2 format, chain G [auth B] MOL2 format, chain I [auth C]	E [auth A], G [auth B], I [auth C]	GENETICIN C₂₀ H₄₀ N₄ O₁₀ BRZYSWJRSDMWLG-DJWUNRQOSA-N		Interactions Focus chain E [auth A] Focus chain G [auth B] Focus chain I [auth C] Interactions & Density Focus chain E [auth A] Focus chain G [auth B] Focus chain I [auth C]
ORX Query on ORX Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain H [auth B] SDF format, chain J [auth C] SDF format, chain K [auth D] MOL2 format, chain F [auth A] MOL2 format, chain H [auth B] MOL2 format, chain J [auth C] MOL2 format, chain K [auth D]	F [auth A], H [auth B], J [auth C], K [auth D]	N~2~-({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)-D-ORNITHINE C₁₃ H₂₂ N₃ O₇ P OIRLUPUXIUAWOH-LLVKDONJSA-N		Interactions Focus chain F [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain K [auth D] Interactions & Density Focus chain F [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain K [auth D]

Binding Affinity Annotations
ID	Source	Binding Affinity
GET	PDBBind: 1NJJ	Ki: 8.00e+6 (nM) from 1 assay(s)
GET	Binding MOAD: 1NJJ	Ki: 8.00e+6 (nM) from 1 assay(s)
ORX	Binding MOAD: 1NJJ	Kd: 2.70e+5 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.45 Å
R-Value Free: 0.283
R-Value Work: 0.260
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 67.818	α = 90
b = 88.54	β = 90.03
c = 150.445	γ = 90

Software Package:

Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
AMoRE	phasing
CNS	refinement

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2003-08-26

Deposition Author(s):

Jackson, L.K.

Goldsmith, E.J.

Phillips, M.A.

Revision History (Full details and data files)

Version 1.0: 2003-08-26
Type: Initial release
Version 1.1: 2008-04-29
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance
Version 1.3: 2018-01-31
Changes: Advisory, Experimental preparation
Version 1.4: 2023-08-16
Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description