PDB-6esq: Structure of the acetoacetyl-CoA thiolase/HMG-CoA synthase comple...

ID or keywords:

Entry

Database: PDB / ID: 6esq

Title

Structure of the acetoacetyl-CoA thiolase/HMG-CoA synthase complex from Methanothermococcus thermolithotrophicus soaked with acetyl-CoA

Components

HydroxyMethylGlutaryl-CoA synthase
Pfam DUF35
acetoacetyl-CoA thiolase

Keywords

TRANSFERASE / Isoprenoid synthesis / enzymatic channeling / mevalonate production / archaea / lipid biosynthesis / multi-enzymatic complex / scaffold protein / DUF35 family

Function / homology

Function and homology information

acetyl-CoA C-acetyltransferase / acetyl-CoA C-acetyltransferase activity / acyltransferase activity
Similarity search - Function

Biological species

Methanothermococcus thermolithotrophicus (archaea)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 2.95 Å

Authors

Voegeli, B. / Engilberge, S. / Girard, E. / Riobe, F. / Maury, O. / Erb, J.T. / Shima, S. / Wagner, T.

Citation

Journal: Proc. Natl. Acad. Sci. U.S.A. / Year: 2018
Title: Archaeal acetoacetyl-CoA thiolase/HMG-CoA synthase complex channels the intermediate via a fused CoA-binding site.
Authors: Vogeli, B. / Engilberge, S. / Girard, E. / Riobe, F. / Maury, O. / Erb, T.J. / Shima, S. / Wagner, T.

History

Deposition	Oct 24, 2017	Deposition site: PDBE / Processing site: PDBE
Revision 1.0	Mar 14, 2018	Provider: repository / Type: Initial release
Revision 1.1	Mar 21, 2018	Group: Database references / Category: citation / citation_author Item: _citation.journal_abbrev / _citation.pdbx_database_id_PubMed ..._citation.journal_abbrev / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2	Apr 11, 2018	Group: Data collection / Database references / Category: citation Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3	May 8, 2024	Group: Data collection / Database references / Derived calculations Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_conn Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr1_symmetry / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_conn.ptnr2_symmetry

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	6esq.cif.gz	2.5 MB	Display	PDBx/mmCIF format
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PDBx/mmJSON format	6esq.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	6esq_validation.pdf.gz	1.7 MB	Display	wwPDB validaton report
Full document	6esq_full_validation.pdf.gz	1.7 MB	Display
Data in XML	6esq_validation.xml.gz	115.6 KB	Display
Data in CIF	6esq_validation.cif.gz	155.5 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/es/6esq ftp://data.pdbj.org/pub/pdb/validation_reports/es/6esq	HTTPS FTP

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Related structure data

Related structure data	6et9C C: citing same article (ref.)
Similar structure data	6et9-d 5mg5-2 5dlq-d 5mg5-1 6941 6qpf-2 1urj-d 6qnw-1 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	#216 - Dec 2017 Biodegradable Plastic similarity (8) #90 - Jun 2007 Fatty Acid Synthase similarity (1) #146 - Feb 2012 Aminoglycoside Antibiotics similarity (1) #93 - Sep 2007 Citrate Synthase similarity (1) #154 - Oct 2012 Citric Acid Cycle similarity (1) #39 - Mar 2003 lac Repressor similarity (1)

Deposited unit

A: acetoacetyl-CoA thiolase

B: acetoacetyl-CoA thiolase

C: acetoacetyl-CoA thiolase

D: acetoacetyl-CoA thiolase

E: Pfam DUF35

F: Pfam DUF35

G: Pfam DUF35

H: Pfam DUF35

I: HydroxyMethylGlutaryl-CoA synthase

J: HydroxyMethylGlutaryl-CoA synthase

K: HydroxyMethylGlutaryl-CoA synthase

L: HydroxyMethylGlutaryl-CoA synthase

hetero molecules

381 kDa, 12 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author&software
Evidence: gel filtration

Unit cell

Length a, b, c (Å)	107.603, 145.176, 230.891
Angle α, β, γ (deg.)	90.00, 90.00, 90.00
Int Tables number	19
Space group name H-M	P2₁2₁2₁

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Protein , 3 types, 12 molecules ABCDEFGHIJKL

#1: Protein	acetoacetyl-CoA thiolase Mass: 41943.410 Da / Num. of mol.: 4 / Mutation: wild-type / Source method: isolated from a natural source / Details: The catalytic Cys85 could be partially acetylated Source: (natural) Methanothermococcus thermolithotrophicus (archaea) Cell line: / / Organ: / / Plasmid details: / / Variant: wild-type / Strain: DSM 2095, strain SN-1 / Tissue: / References: UniProt: A0A384E138*PLUS, acetyl-CoA C-acetyltransferase
#2: Protein	Pfam DUF35 Mass: 14910.377 Da / Num. of mol.: 4 / Mutation: wild-type / Source method: isolated from a natural source Source: (natural) Methanothermococcus thermolithotrophicus (archaea) Cell line: / / Organ: / / Plasmid details: / / Variant: wild-type / Strain: DSM 2095, strain SN-1 / Tissue: / / References: UniProt: A0A384E139*PLUS
#3: Protein	HydroxyMethylGlutaryl-CoA synthase Mass: 37520.570 Da / Num. of mol.: 4 / Mutation: wild-type / Source method: isolated from a natural source / Details: The catalytic Cys114 could be partially acetylated Source: (natural) Methanothermococcus thermolithotrophicus (archaea) Cell line: / / Organ: / / Plasmid details: / / Variant: wild-type / Strain: DSM 2095, strain SN-1 / Tissue: / References: UniProt: A0A384E143*PLUS, hydroxymethylglutaryl-CoA synthase

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Non-polymers , 6 types, 77 molecules

#4: Chemical	ChemComp-COA / COENZYME A Mass: 767.534 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C₂₁H₃₆N₇O₁₆P₃S
#5: Chemical	ChemComp-K / POTASSIUM ION Mass: 39.098 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: K
#6: Chemical	ChemComp-ZN / ZINC ION Mass: 65.409 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Zn
#7: Chemical	ChemComp-CL / CHLORIDE ION Mass: 35.453 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Cl
#8: Chemical	ChemComp-NA / SODIUM ION Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#9: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 61 / Source method: isolated from a natural source / Formula: H₂O

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Experiment

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

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Sample preparation

Crystal	Density Matthews: 2.3 Å³/Da / Density % sol: 46.53 % Description: Transparent square crystal of about 100 micron cube.
Crystal grow	Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: Crystallization was done under air using the sitting drop method (in a 24-well junior clover plate from Jena Bioscience). The crystallization reservoir contained 100 mM Tris/HCl pH 8.0, 25- ...Details: Crystallization was done under air using the sitting drop method (in a 24-well junior clover plate from Jena Bioscience). The crystallization reservoir contained 100 mM Tris/HCl pH 8.0, 25-28% v/v pentaerythritol ethoxylate (15/4 EO/OH, average Mn about 797) and 50 mM MgCl2. Crystallization drop contained 1 to 2 ul of the purified fraction containing Thiolase/HMGCS complex at 50-60 mg/ml (pure at 60%) and 1 ul of precipitant. The crystal was soaked in the crystallization condition supplemented 100 mM acetyl-CoA for 1 min 30 sec. PH range: 8.0-9.0 / Temp details: 290-295

Crystal

Density Matthews: 2.3 Å³/Da / Density % sol: 46.53 %
Description: Transparent square crystal of about 100 micron cube.

Crystal grow

Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: Crystallization was done under air using the sitting drop method (in a 24-well junior clover plate from Jena Bioscience). The crystallization reservoir contained 100 mM Tris/HCl pH 8.0, 25- ...
PH range: 8.0-9.0 / Temp details: 290-295

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Data collection

Diffraction	Mean temperature: 100 K
Diffraction source	Source: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 1.64861 Å
Detector	Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 27, 2016
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1.64861 Å / Relative weight: 1
Reflection	Resolution: 2.95→49.3 Å / Num. obs: 76363 / % possible obs: 99.4 % / Redundancy: 13.3 % / B_iso Wilson estimate: 97.33 Å² / CC_1/2: 0.999 / R_merge(I) obs: 0.143 / R_pim(I) all: 0.04 / Net I/av σ(I): 14.9 / Net I/σ(I): 14.9
Reflection shell	Resolution: 2.95→3.11 Å / Redundancy: 13.1 % / R_merge(I) obs: 2.024 / Mean I/σ(I) obs: 1.3 / Num. unique obs: 10942 / CC_1/2: 0.481 / R_pim(I) all: 0.577 / % possible all: 98.8

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Processing

Software

Name	Version	Classification
BUSTER	2.10.3	refinement
XDS		data reduction
SCALA		data scaling
PHASER		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT / Resolution: 2.95→49.29 Å / Cor.coef. F_o:F_c: 0.935 / Cor.coef. F_o:F_c free: 0.918 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R_free Blow DPI: 0.389

	R_factor	Num. reflection	% reflection	Selection details
R_free	0.23	3807	4.99 %	RANDOM
R_work	0.182	-	-	-
obs	0.184	76299	99.3 %	-

Displacement parameters

B_iso mean: 106.71 Å²

	B_aniso -1	B_aniso -2	B_aniso -3
1-	1.0066 Å²	0 Å²	0 Å²
2-	-	-15.6281 Å²	0 Å²
3-	-	-	14.6215 Å²

Refine analyze

Luzzati coordinate error obs: 0.35 Å

Refinement step

Cycle: 1 / Resolution: 2.95→49.29 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	26334	0	172	61	26567

Refine LS restraints

Refine-ID	Type	Dev ideal	Number	Restraint function	Weight
X-RAY DIFFRACTION	t_bond_d	0.005	53258	HARMONIC	12
X-RAY DIFFRACTION	t_angle_deg	0.58	96394	HARMONIC	12
X-RAY DIFFRACTION	t_dihedral_angle_d		11788	SINUSOIDAL	2
X-RAY DIFFRACTION	t_incorr_chiral_ct
X-RAY DIFFRACTION	t_pseud_angle
X-RAY DIFFRACTION	t_trig_c_planes		613	HARMONIC	2
X-RAY DIFFRACTION	t_gen_planes		7838	HARMONIC	5
X-RAY DIFFRACTION	t_it		53258	HARMONIC	20
X-RAY DIFFRACTION	t_nbd		17	SEMIHARMONIC	5
X-RAY DIFFRACTION	t_omega_torsion	5.03
X-RAY DIFFRACTION	t_other_torsion	15.01
X-RAY DIFFRACTION	t_improper_torsion
X-RAY DIFFRACTION	t_chiral_improper_torsion		3593	SEMIHARMONIC	5
X-RAY DIFFRACTION	t_sum_occupancies
X-RAY DIFFRACTION	t_utility_distance
X-RAY DIFFRACTION	t_utility_angle
X-RAY DIFFRACTION	t_utility_torsion
X-RAY DIFFRACTION	t_ideal_dist_contact		59603	SEMIHARMONIC	4

LS refinement shell

Resolution: 2.95→3.03 Å / Total num. of bins used: 20

	R_factor	Num. reflection	% reflection
R_free	0.2819	283	5.14 %
R_work	0.2365	5226	-
all	0.2389	5509	-
obs	-	-	98.31 %

Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

ID	L11 (°²)	L12 (°²)	L13 (°²)	L22 (°²)	L23 (°²)	L33 (°²)	S11 (Å °)	S12 (Å °)	S13 (Å °)	S21 (Å °)	S22 (Å °)	S23 (Å °)	S31 (Å °)	S32 (Å °)	S33 (Å °)	T11 (Å²)	T12 (Å²)	T13 (Å²)	T22 (Å²)	T23 (Å²)	T33 (Å²)	Origin x (Å)	Origin y (Å)	Origin z (Å)
1	1.1019	0.4546	-1.8124	1.1242	0.0787	0	0.03	0.1343	-0.1843	0.0893	0.034	-0.0089	0.0429	0.2042	-0.0639	0.0639	0.152	0.152	0.2699	-0.152	-0.2569	83.0988	16.3862	12.212
2	1.0132	-0.1873	0.8725	1.0477	-0.5753	1.5833	-0.0599	-0.1147	-0.1035	0.0146	-0.0267	0.0461	-0.32	0.1435	0.0866	0.0728	-0.0229	-0.0932	-0.1855	0.0326	-0.0374	74.1778	51.7049	102.937
3	0.0362	1.0992	0.5204	0.0756	0.8174	1.8729	-0.016	0.1101	0.0131	-0.1555	-0.0761	0.0472	-0.1625	-0.0074	0.0921	0.1182	-0.1305	0.1467	0.1809	0.1494	-0.2841	72.7308	49.7057	9.6305
4	1.1507	-0.7282	-0.2003	1.197	0.2564	1.4012	0.1163	-0.0099	0.0033	-0.0104	-0.1323	-0.1239	0.1558	-0.2476	0.0159	0.0371	0.0097	0.0022	-0.1406	0.1367	-0.0249	56.9299	21.3077	101.831
5	1.5719	-0.4664	-0.1409	0.2347	-1.0156	0.0018	0.0039	0.0375	0.0188	0.033	0.0145	-0.0164	0.0005	0.0872	-0.0185	-0.0411	0.152	0.0128	0.1111	0.0848	-0.0406	84.5633	17.3644	86.0483
6	0.2043	-1.1354	-0.493	2.0199	0.7565	2.6487	-0.0001	0.09	0.0001	-0.0421	0.0193	0.0293	0.0592	0.0334	-0.0192	0.1849	-0.0562	-0.0524	-0.2649	-0.0953	-0.0381	55.3696	19.3436	28.25
7	0.501	0.4853	0.2056	1.0895	0.6792	1.7318	-0.0147	-0.0072	0.0137	0.0438	0.0112	0.0359	-0.0837	-0.0584	0.0035	0.1195	0.0879	-0.0851	-0.2109	-0.0194	-0.0032	51.76	53.9023	79.9493
8	0.5382	-0.1976	-0.7915	0	-1.6879	2.8358	0.0062	0.003	-0.021	-0.0087	-0.006	-0.0093	-0.0009	0.015	-0.0001	-0.0397	-0.1195	0.152	0.1996	0.0717	-0.1397	95.2931	48.2204	32.5715
9	1.4302	0.1078	0.2879	0.9025	-0.1005	1.4789	-0.0239	-0.0234	0.1144	-0.1797	-0.0564	0.2218	-0.2606	0.0259	0.0803	0.1074	0.0381	-0.0885	-0.271	0.0052	0.0381	47.0956	53.4188	49.5112
10	1.8598	-1.0499	0.7994	0.8227	-0.0214	0	0.0177	-0.0838	-0.1418	-0.2243	-0.0671	-0.0145	0.1042	0.1473	0.0494	-0.2607	0.152	0.1446	0.304	0.0561	-0.0741	97.25	15.835	57.7512
11	1.6866	-0.1015	0.3336	1.152	0.0533	1.9294	0.0073	-0.0902	-0.094	-0.0762	-0.0889	0.1592	0.2844	-0.1595	0.0817	0.085	-0.1146	-0.0297	-0.2721	-0.0016	0.0006	42.7507	22.0482	56.1818
12	2.3619	-0.0121	0.3174	1.2297	-0.2472	0.4569	0.0191	0.0347	0.1059	-0.016	-0.1762	-0.095	-0.062	0.1886	0.1571	-0.2967	-0.152	0.0661	0.3028	0.152	-0.1582	100.091	47.6328	63.0876
13	0	-0.4016	0.01	0	-0.8131	0	-0.0003	-0.0035	-0.0099	-0.0004	-0.0048	-0.0086	-0.0069	-0.0142	0.0051	-0.0134	0.0125	0.0015	-0.0002	-0.006	-0.0201	72.0106	34.5537	57.1315

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	{ A\|* }
2	X-RAY DIFFRACTION	2	{ B\|* }
3	X-RAY DIFFRACTION	3	{ C\|* }
4	X-RAY DIFFRACTION	4	{ D\|* }
5	X-RAY DIFFRACTION	5	{ E\|* }
6	X-RAY DIFFRACTION	6	{ F\|* }
7	X-RAY DIFFRACTION	7	{ G\|* }
8	X-RAY DIFFRACTION	8	{ H\|* }
9	X-RAY DIFFRACTION	9	{ I\|* }
10	X-RAY DIFFRACTION	10	{ J\|* }
11	X-RAY DIFFRACTION	11	{ K\|* }
12	X-RAY DIFFRACTION	12	{ L\|* }
13	X-RAY DIFFRACTION	13	{ P\|* }

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