1SJ2

Crystal structure of Mycobacterium tuberculosis catalase-peroxidase

PDB DOI: https://doi.org/10.2210/pdb1SJ2/pdb

Classification: OXIDOREDUCTASE
Organism(s): Mycobacterium tuberculosis
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2004-03-02 Released: 2004-07-20
Deposition Author(s): Bertrand, T., Eady, N.A.J., Jones, J.N., Bodiguel, J., Jesmin, Nagy, J.M., Raven, E.L., Jamart-Gregoire, B., Brown, K.A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.41 Å
R-Value Free: 0.268
R-Value Work: 0.211

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Crystal Structure of Mycobacterium tuberculosis Catalase-Peroxidase.

Bertrand, T., Eady, N.A.J., Jones, J.N., Jesmin, Nagy, J.M., Jamart-Gregoire, B., Raven, E.L., Brown, K.A.

(2004) J Biol Chem 279: 38991-38999

PubMed: 15231843 Search on PubMed
DOI: https://doi.org/10.1074/jbc.M402382200
Primary Citation of Related Structures:
1SJ2

PubMed Abstract:
The Mycobacterium tuberculosis catalase-peroxidase is a multifunctional heme-dependent enzyme that activates the core anti-tuberculosis drug isoniazid. Numerous studies have been undertaken to elucidate the enzyme-dependent mechanism of isoniazid activation, and it is well documented that mutations that reduce activity or inactivate the catalase-peroxidase lead to increased levels of isoniazid resistance in M. tuberculosis. Interpretation of the catalytic activities and the effects of mutations upon the action of the enzyme to date have been limited due to the lack of a three-dimensional structure for this enzyme. In order to provide a more accurate model of the three-dimensional structure of the M. tuberculosis catalase-peroxidase, we have crystallized the enzyme and now report its crystal structure refined to 2.4-A resolution. The structure reveals new information about dimer assembly and provides information about the location of residues that may play a role in catalysis including candidates for protein-based radical formation. Modeling and computational studies suggest that the binding site for isoniazid is located near the delta-meso heme edge rather than in a surface loop structure as currently proposed. The availability of a crystal structure for the M. tuberculosis catalase-peroxidase also permits structural and functional effects of mutations implicated in causing elevated levels of isoniazid resistance in clinical isolates to be interpreted with improved confidence.

Organizational Affiliation

Department of Biological Sciences, Centre for Molecular Microbiology and Infection, Flowers Building, Imperial College London, London SW7 2AZ, United Kingdom.

Macromolecule Content

Total Structure Weight: 163.91 kDa
Atom Count: 11,883
Modelled Residue Count: 1,434
Deposited Residue Count: 1,486
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Peroxidase/catalase T	A, B	743	Mycobacterium tuberculosis	Mutation(s): 0 Gene Names: KATG, RV1908C, MT1959, MTCY180.10 EC: 1.11.1.6
UniProt
Find proteins for P9WIE5 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)) Explore P9WIE5 Go to UniProtKB: P9WIE5
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P9WIE5
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
HEM Query on HEM Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain G [auth B] MOL2 format, chain C [auth A] MOL2 format, chain G [auth B]	C [auth A], G [auth B]	PROTOPORPHYRIN IX CONTAINING FE C₃₄ H₃₂ Fe N₄ O₄ KABFMIBPWCXCRK-RGGAHWMASA-L		Interactions Focus chain C [auth A] Focus chain G [auth B] Interactions & Density Focus chain C [auth A] Focus chain G [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain H [auth B] SDF format, chain I [auth B] SDF format, chain J [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B] MOL2 format, chain J [auth B]	D [auth A] E [auth A] F [auth A] H [auth B] I [auth B] D [auth A], E [auth A], F [auth A], H [auth B], I [auth B], J [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain H [auth B] Focus chain I [auth B] Focus chain J [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain H [auth B] Focus chain I [auth B] Focus chain J [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.41 Å
R-Value Free: 0.268
R-Value Work: 0.211
Space Group: P 4₂ 2₁ 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 150.33	α = 90
b = 150.33	β = 90
c = 154.281	γ = 90

Software Package:

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

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2004-07-20

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2004-07-20
Type: Initial release
Version 1.1: 2008-04-29
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Non-polymer description, Version format compliance
Version 1.3: 2023-08-23
Changes: Data collection, Database references, Derived calculations, Refinement description