PDB-6xpp: Crystal structure of itaconate modified Mycobaterium tuberculosis...

ID or keywords:

Entry

Database: PDB / ID: 6xpp

Title

Crystal structure of itaconate modified Mycobaterium tuberculosis isocitrate lyase

Components

Isocitrate lyase

Keywords

LYASE / covalent modification

Function / homology

Function and homology information

isocitrate lyase / methylisocitrate lyase activity / isocitrate lyase activity / isocitrate metabolic process / glyoxylate cycle / zymogen binding / tricarboxylic acid cycle / cellular response to hypoxia / extracellular region / metal ion binding ...
Similarity search - Function

Biological species

Mycobacterium tuberculosis (bacteria)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.55 Å

Authors

Kwai, B.X.C. / Bashiri, G. / Leung, I.K.H.

Funding support

New Zealand, 2items

Citation

Journal: Rsc Med Chem / Year: 2021
Title: Itaconate is a covalent inhibitor of the Mycobacterium tuberculosis isocitrate lyase.
Authors: Kwai, B.X.C. / Collins, A.J. / Middleditch, M.J. / Sperry, J. / Bashiri, G. / Leung, I.K.H.

History

Deposition	Jul 8, 2020	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Oct 21, 2020	Provider: repository / Type: Initial release
Revision 1.1	Jun 9, 2021	Group: Database references / Category: citation / citation_author Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2	Oct 18, 2023	Group: Data collection / Database references / Refinement description Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	6xpp.cif.gz	382.9 KB	Display	PDBx/mmCIF format
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Validation report

Summary document	6xpp_validation.pdf.gz	5.2 MB	Display	wwPDB validaton report
Full document	6xpp_full_validation.pdf.gz	5.2 MB	Display
Data in XML	6xpp_validation.xml.gz	76.9 KB	Display
Data in CIF	6xpp_validation.cif.gz	114.8 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/xp/6xpp ftp://data.pdbj.org/pub/pdb/validation_reports/xp/6xpp	HTTPS FTP

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Related structure data

Related structure data	1f8iS S: Starting model for refinement
Similar structure data	6c4a-1 6c4a-2 5dql-d 1f8i-d 6c4c-1 6c4c-2 6wsi-d 1f61-1 6vb9-d 4r68-d Search similar-shape structures by Omokage search (details) Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

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Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#50 - Feb 2004 Glycolytic Enzymes similarity (2)

Deposited unit

A: Isocitrate lyase

B: Isocitrate lyase

C: Isocitrate lyase

D: Isocitrate lyase

hetero molecules

189 kDa, 4 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author&software

Unit cell

Length a, b, c (Å)	79.314, 133.171, 159.318
Angle α, β, γ (deg.)	90.000, 90.000, 90.000
Int Tables number	19
Space group name H-M	P2₁2₁2₁

Noncrystallographic symmetry (NCS)

NCS domain:

ID	Ens-ID	Details
1	1	Chains A B
2	2	Chains A C
3	3	Chains A D
4	4	Chains B C
5	5	Chains B D
6	6	Chains C D

NCS ensembles :

ID
1
2
3
4
5
6

#1: Protein	Isocitrate lyase / ICL / Isocitrase / Isocitratase Mass: 47134.391 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) (bacteria) Strain: ATCC 25618 / H37Rv / Gene: icl, Rv0467, MTV038.11 / Production host: Escherichia coli (E. coli) / References: UniProt: P9WKK7, isocitrate lyase
#2: Chemical	ChemComp-ITN / 2-methylidenebutanedioic acid Mass: 130.099 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₅H₆O₄ / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-MG / MAGNESIUM ION Mass: 24.305 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: Mg / Feature type: SUBJECT OF INVESTIGATION
#4: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 1770 / Source method: isolated from a natural source / Formula: H₂O
Has ligand of interest	Y

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Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal	Density Matthews: 2.23 Å³/Da / Density % sol: 44.88 %
Crystal grow	Temperature: 291 K / Method: vapor diffusion, sitting drop / pH: 7.5 Details: 20% PEG3350, 0.2M sodium nitrate, 0.1M bis-tris propane

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.953733 Å
Detector	Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Aug 8, 2019
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.953733 Å / Relative weight: 1
Reflection	Resolution: 1.55→49.377 Å / Num. obs: 242871 / % possible obs: 99.7 % / Redundancy: 13.8 % / CC_1/2: 0.999 / R_merge(I) obs: 0.123 / R_pim(I) all: 0.034 / R_rim(I) all: 0.128 / Χ²: 0.99 / Net I/σ(I): 11.6
Reflection shell	Resolution: 1.55→1.58 Å / Redundancy: 14.1 % / R_merge(I) obs: 2.057 / Mean I/σ(I) obs: 1.4 / Num. unique obs: 11809 / CC_1/2: 0.613 / R_pim(I) all: 0.56 / R_rim(I) all: 2.133 / Χ²: 1.05 / % possible all: 99

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Processing

Software

Name	Version	Classification
REFMAC	5.8.0258	refinement
XDS		data reduction
Aimless		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 1F8I

1f8i

Resolution: 1.55→49.377 Å / Cor.coef. F_o:F_c: 0.974 / Cor.coef. F_o:F_c free: 0.97 / WR_factor R_free: 0.171 / WR_factor R_work: 0.151 / SU B: 1.594 / SU ML: 0.055 / Average fsc free: 0.9317 / Average fsc work: 0.9355 / Cross valid method: FREE R-VALUE / ESU R: 0.074 / ESU R Free: 0.072
Details: Hydrogens have been added in their riding positions

	R_factor	Num. reflection	% reflection
R_free	0.1791	12123	4.994 %
R_work	0.1584	230624	-
all	0.159	-	-
obs	-	242747	99.574 %

Solvent computation

Ion probe radii: 0.9 Å / Shrinkage radii: 0.9 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT

Displacement parameters

B_iso mean: 21.236 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	-0.679 Å²	-0 Å²	-0 Å²
2-	-	-0.093 Å²	0 Å²
3-	-	-	0.773 Å²

Refinement step

Cycle: LAST / Resolution: 1.55→49.377 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	13198	0	44	1770	15012

Refine LS restraints

Refine-ID	Type	Dev ideal	Dev ideal target	Number
X-RAY DIFFRACTION	r_bond_refined_d	0.005	0.013	13579
X-RAY DIFFRACTION	r_bond_other_d	0.001	0.017	12194
X-RAY DIFFRACTION	r_angle_refined_deg	1.303	1.643	18478
X-RAY DIFFRACTION	r_angle_other_deg	1.427	1.576	28259
X-RAY DIFFRACTION	r_dihedral_angle_1_deg	6.285	5	1719
X-RAY DIFFRACTION	r_dihedral_angle_2_deg	33.359	22.891	754
X-RAY DIFFRACTION	r_dihedral_angle_3_deg	11.779	15	2156
X-RAY DIFFRACTION	r_dihedral_angle_4_deg	17.312	15	86
X-RAY DIFFRACTION	r_chiral_restr	0.069	0.2	1788
X-RAY DIFFRACTION	r_chiral_restr_other	0.016	0.2	8
X-RAY DIFFRACTION	r_gen_planes_refined	0.006	0.02	15607
X-RAY DIFFRACTION	r_gen_planes_other	0.001	0.02	2903
X-RAY DIFFRACTION	r_nbd_refined	0.208	0.2	2823
X-RAY DIFFRACTION	r_symmetry_nbd_other	0.174	0.2	11762
X-RAY DIFFRACTION	r_nbtor_refined	0.161	0.2	6751
X-RAY DIFFRACTION	r_symmetry_nbtor_other	0.077	0.2	5362
X-RAY DIFFRACTION	r_xyhbond_nbd_refined	0.127	0.2	1339
X-RAY DIFFRACTION	r_symmetry_nbd_refined	0.181	0.2	10
X-RAY DIFFRACTION	r_nbd_other	0.207	0.2	38
X-RAY DIFFRACTION	r_symmetry_xyhbond_nbd_refined	0.11	0.2	11
X-RAY DIFFRACTION	r_mcbond_it	1.833	2.033	6825
X-RAY DIFFRACTION	r_mcbond_other	1.826	2.032	6824
X-RAY DIFFRACTION	r_mcangle_it	2.399	3.046	8528
X-RAY DIFFRACTION	r_mcangle_other	2.399	3.047	8529
X-RAY DIFFRACTION	r_scbond_it	3.098	2.362	6754
X-RAY DIFFRACTION	r_scbond_other	3.099	2.362	6752
X-RAY DIFFRACTION	r_scangle_it	4.597	3.416	9939
X-RAY DIFFRACTION	r_scangle_other	4.596	3.416	9939
X-RAY DIFFRACTION	r_lrange_it	5.375	25.679	16240
X-RAY DIFFRACTION	r_lrange_other	5.277	24.976	15748
X-RAY DIFFRACTION	r_ncsr_local_group_1	0.047	0.05	14105
X-RAY DIFFRACTION	r_ncsr_local_group_2	0.056	0.05	14057
X-RAY DIFFRACTION	r_ncsr_local_group_3	0.048	0.05	14100
X-RAY DIFFRACTION	r_ncsr_local_group_4	0.058	0.05	13887
X-RAY DIFFRACTION	r_ncsr_local_group_5	0.05	0.05	13975
X-RAY DIFFRACTION	r_ncsr_local_group_6	0.047	0.05	14042

LS refinement shell

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Refine-ID	% reflection obs (%)
1.55-1.59	0.27	860	0.272	16800	X-RAY DIFFRACTION	98.8746
1.59-1.634	0.267	808	0.254	16444	X-RAY DIFFRACTION	99.0356
1.634-1.681	0.248	869	0.237	15921	X-RAY DIFFRACTION	99.0911
1.681-1.733	0.242	810	0.216	15531	X-RAY DIFFRACTION	99.1746
1.733-1.79	0.226	809	0.198	15075	X-RAY DIFFRACTION	99.3433
1.79-1.853	0.218	780	0.189	14641	X-RAY DIFFRACTION	99.4775
1.853-1.922	0.206	764	0.176	14070	X-RAY DIFFRACTION	99.5704
1.922-2.001	0.209	743	0.168	13607	X-RAY DIFFRACTION	99.7082
2.001-2.09	0.185	657	0.159	13136	X-RAY DIFFRACTION	99.7685
2.09-2.192	0.183	664	0.154	12515	X-RAY DIFFRACTION	99.8333
2.192-2.31	0.173	647	0.143	11944	X-RAY DIFFRACTION	99.8889
2.31-2.45	0.166	601	0.141	11300	X-RAY DIFFRACTION	99.9832
2.45-2.619	0.158	586	0.133	10656	X-RAY DIFFRACTION	99.9911
2.619-2.829	0.173	502	0.141	9988	X-RAY DIFFRACTION	100
2.829-3.099	0.181	484	0.148	9152	X-RAY DIFFRACTION	100
3.099-3.464	0.171	429	0.156	8357	X-RAY DIFFRACTION	100
3.464-3.999	0.148	375	0.14	7404	X-RAY DIFFRACTION	100
3.999-4.896	0.138	323	0.125	6282	X-RAY DIFFRACTION	100
4.896-6.917	0.171	263	0.154	4954	X-RAY DIFFRACTION	100
6.917-49.377	0.145	149	0.161	2848	X-RAY DIFFRACTION	99.502

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