PDB-8fqq: ADC-162 in complex with boronic acid transition state inhibitor MB076

ID or keywords:

Entry

Database: PDB / ID: 8fqq

Title

ADC-162 in complex with boronic acid transition state inhibitor MB076

Components

Beta-lactamase

Keywords

HYDROLASE/HYDROLASE INHIBITOR / BATSI / inhibitor / Acinetobacter-derived cephalosporinase / HYDROLASE / HYDROLASE-HYDROLASE INHIBITOR complex

Function / homology

Function and homology information

antibiotic catabolic process / beta-lactamase activity / beta-lactamase / outer membrane-bounded periplasmic space / response to antibiotic
Similarity search - Function

Biological species

Acinetobacter baumannii (bacteria)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 1.48 Å

Authors

Powers, R.A. / Wallar, B.J. / June, C.M. / Fernando, M.C.

Funding support

United States, 1items

Citation

Journal: J.Med.Chem. / Year: 2023
Title: Synthesis of a Novel Boronic Acid Transition State Inhibitor, MB076: A Heterocyclic Triazole Effectively Inhibits Acinetobacter -Derived Cephalosporinase Variants with an Expanded-Substrate Spectrum.
Authors: Powers, R.A. / June, C.M. / Fernando, M.C. / Fish, E.R. / Maurer, O.L. / Baumann, R.M. / Beardsley, T.J. / Taracila, M.A. / Rudin, S.D. / Hujer, K.M. / Hujer, A.M. / Santi, N. / Villamil, V. ...

History

Deposition	Jan 6, 2023	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	Jul 5, 2023	Provider: repository / Type: Initial release
Revision 1.1	Jul 12, 2023	Group: Database references / Category: citation / Item: _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2	Jul 26, 2023	Group: Database references / Category: citation Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3	Oct 25, 2023	Group: Data collection / Category: chem_comp_atom / chem_comp_bond

Structure viewer	Molecule: MolmilJmol/JSmol

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Download

PDBx/mmCIF format	8fqq.cif.gz	311.6 KB	Display	PDBx/mmCIF format
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PDBx/mmJSON format	8fqq.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Summary document	8fqq_validation.pdf.gz	1009.7 KB	Display	wwPDB validaton report
Full document	8fqq_full_validation.pdf.gz	1013.6 KB	Display
Data in XML	8fqq_validation.xml.gz	34 KB	Display
Data in CIF	8fqq_validation.cif.gz	51.6 KB	Display
Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/fq/8fqq ftp://data.pdbj.org/pub/pdb/validation_reports/fq/8fqq	HTTPS FTP

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Related structure data

Related structure data	8fqmC 8fqnC 8fqoC 8fqpC 8fqrC 8fqsC 8fqtC 8fquC 8fqvC 8fqwC 4u0xS S: Starting model for refinement C: citing same article (ref.)
Similar structure data	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	#29 - May 2002 Penicillin-binding Proteins similarity (2) #235 - Jul 2019 AMPA Receptor similarity (1) #142 - Oct 2011 PDB Pioneers similarity (1)

Deposited unit

A: Beta-lactamase

B: Beta-lactamase

hetero molecules

82.5 kDa, 2 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

A: Beta-lactamase

hetero molecules

defined by author
Evidence: monomeric biological assembly
41.2 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

2

B: Beta-lactamase

hetero molecules

defined by author
41.3 kDa, 1 polymers
Search similar-shape structures of this assembly by Omokage search (details)

Unit cell

Length a, b, c (Å)	43.166, 83.286, 209.167
Angle α, β, γ (deg.)	90.00, 90.00, 90.00
Int Tables number	19
Space group name H-M	P2₁2₁2₁

#1: Protein	Beta-lactamase Mass: 40728.430 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Acinetobacter baumannii (bacteria) / Gene: blaADC / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: A0A2H4PPJ8
#2: Chemical	ChemComp-YDB / 1-[(2R)-2-{2-[(5-amino-1,3,4-thiadiazol-2-yl)sulfanyl]acetamido}-2-boronoethyl]-1H-1,2,3-triazole-4-carboxylic acid Mass: 373.176 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₉H₁₂BN₇O₅S₂ / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical	ChemComp-PO4 / PHOSPHATE ION Mass: 94.971 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Formula: PO₄
#4: Chemical	ChemComp-GLY / GLYCINE Type: peptide linking / Mass: 75.067 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C₂H₅NO₂
#5: Water	ChemComp-HOH / water Mass: 18.015 Da / Num. of mol.: 681 / 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: 2.31 Å³/Da / Density % sol: 46.71 %
Crystal grow	Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 5 / Details: 0.1 M SPG, 25% w/v PEG 1500

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Data collection

Diffraction	Mean temperature: 100 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-D / Wavelength: 0.99984 Å
Detector	Type: DECTRIS EIGER X 9M / Detector: PIXEL / Date: Jul 17, 2019
Radiation	Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 0.99984 Å / Relative weight: 1
Reflection	Resolution: 1.48→77.38 Å / Num. obs: 78568 / % possible obs: 89.5 % / Redundancy: 5 % / CC_1/2: 0.999 / R_pim(I) all: 0.034 / Net I/σ(I): 12
Reflection shell	Resolution: 1.48→1.6 Å / Num. unique obs: 3828 / CC_1/2: 0.501 / R_pim(I) all: 0.444

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Processing

Software

Name	Version	Classification
Aimless		data scaling
PHASER		phasing
PHENIX	v1.19	refinement
Coot		model building
autoPROC		data reduction

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 4U0X

4u0x

Resolution: 1.48→37.38 Å / SU ML: 0.18 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 30.93 / Stereochemistry target values: ML

	R_factor	Num. reflection	% reflection
R_free	0.25	4023	5.12 %
R_work	0.2105	-	-
obs	0.2125	78556	62.33 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL

Refinement step

Cycle: LAST / Resolution: 1.48→37.38 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	5674	0	63	681	6418

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.002	5950
X-RAY DIFFRACTION	f_angle_d	0.476	8077
X-RAY DIFFRACTION	f_dihedral_angle_d	11.986	2247
X-RAY DIFFRACTION	f_chiral_restr	0.065	877
X-RAY DIFFRACTION	f_plane_restr	0.004	1044

LS refinement shell

Resolution: 1.484→1.599 Å

	R_factor	Num. reflection	% reflection
R_free	0.191	209	-
R_work	0.1665	3758	-
obs	-	-	84 %

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	0.6353	0.2364	-0.3407	0.84	-0.018	0.6528	-0.0184	0.0058	0.0409	-0.1498	0.0189	-0.1165	-0.0523	0.0435	0.0001	0.0994	0.0071	0.026	0.0455	-0.0136	0.0957	19.6995	25.1412	-48.0155
2	0.3545	0.0933	-0.052	0.3975	-0.1397	0.51	-0.011	-0.3051	-0.1683	0.2814	-0.0402	-0.0246	0.1516	-0.0295	0.0258	0.2375	-0.0123	0.0746	0.2043	0.0959	0.1309	8.4485	-3.5312	-28.8577
3	0.9413	-0.0831	-0.1715	1.1668	-0.2119	1.4785	-0.041	-0.2093	-0.0603	0.1879	0.0728	0.1426	0.0628	-0.092	-0.0308	0.1552	-0.0006	0.0393	0.1289	-0.0002	0.1454	-2.1943	7.1411	-31.7716
4	0.7151	-0.1989	-0.2446	0.7882	-0.4748	0.8327	0.0006	-0.198	-0.1573	0.0938	-0.0313	0.0293	0.1195	-0.0388	0.0327	0.1306	-0.0068	0.0415	0.1081	0.0216	0.1385	3.8309	1.2501	-36.0114
5	0.946	-0.1882	0.2129	0.8692	0.0697	0.5352	-0.0531	-0.2888	0.1484	0.3563	0.0396	-0.2294	-0.0338	-0.0592	0.0141	0.1685	0.0182	-0.0192	0.1736	-0.0281	0.146	19.6597	17.1777	-28.7623
6	0.5098	-0.005	-0.1173	0.9444	0.094	0.6224	0.0073	-0.1693	-0.0289	0.1585	-0.013	0.0916	-0.0563	-0.0417	-0.0005	0.098	-0.0058	0.0294	0.0955	-0.0296	0.0955	12.3619	23.8019	-37.9141
7	1.1066	0.5518	0.09	0.8201	-0.2967	0.8571	0.0655	-0.1615	-0.114	0.0609	-0.0774	-0.1206	0.1143	0.077	0.0397	0.0987	0.0255	0.0178	0.0898	0.0205	0.1	21.1389	3.2175	-43.7024
8	0.3268	0.3714	-0.3732	0.8036	-0.1673	0.7238	-0.0397	0.0813	-0.022	-0.0704	-0.0323	0.0612	0.0254	-0.025	0.0371	0.1118	-0.013	0.0192	0.0554	-0.0097	0.1339	10.4038	3.091	-54.6932
9	0.7157	-0.0959	0.0691	0.8088	0.0909	0.5361	-0.0162	-0.091	-0.036	0.0031	0.0437	-0.082	0.0944	0.031	0.0277	0.1023	0.0154	0.0282	0.047	-0.0162	0.1063	17.127	13.8221	-48.9132
10	0.5786	-0.0072	0.1071	1.2104	0.4313	0.9972	-0.0665	0.1147	-0.1024	-0.1548	-0.0104	-0.0437	0.0218	-0.0043	0.057	0.1139	-0.0022	0.0391	0.0517	-0.0015	0.131	16.9135	19.447	-54.7069
11	0.9196	-0.0718	-0.17	1.1028	-0.2429	0.956	0.0507	0.0205	-0.59	-0.1263	-0.012	0.0277	0.5627	-0.1432	0.0248	0.2974	-0.049	0.0074	0.1521	0.039	0.3067	2.6331	-11.3227	-81.0095
12	0.296	0.0634	-0.1976	0.5004	-0.5255	1.0606	0.0457	0.1942	0.0916	0.0322	-0.0371	-0.0015	-0.0924	0.0402	-0.0585	0.0962	-0.0226	0.008	0.2166	0.1626	0.0422	8.761	14.8251	-86.3717
13	0.3527	0.1915	-0.0354	0.9955	-0.0921	0.685	0.0646	0.1472	0.2691	0.139	-0.1257	-0.0382	-0.1678	0.1704	-0.0017	0.1419	-0.0658	0.0014	0.3188	0.0902	0.1842	23.4163	22.7737	-89.198
14	0.4885	-0.1213	-0.1092	0.2923	-0.249	0.5934	0.0978	0.1563	0.2592	0.0971	0.0053	0.0493	-0.1776	-0.0401	-0.0102	0.1307	0.0078	0.0382	0.2057	0.1211	0.1389	1.814	19.381	-84.7683
15	0.7174	-0.0815	0.2291	0.5624	-0.3194	1.3605	-0.0254	0.0051	-0.0331	0.124	0.0187	0.0126	-0.0837	0.055	0.0219	0.094	-0.0172	0.0145	0.1745	0.0488	0.1017	4.7676	8.0401	-76.1256
16	0.6826	-0.0591	-0.02	0.2419	-0.2114	0.2439	0.0111	0.3853	0.1075	-0.1031	-0.0225	-0.0013	0.0509	-0.0186	-0.0863	0.1259	-0.0084	-0.0175	0.3879	0.0773	0.0588	5.3231	9.3451	-99.1476
17	0.7382	-0.0939	0.0138	1.1672	-0.1412	0.686	-0.2169	0.4598	-0.3846	-0.0706	0.0458	-0.1482	0.1217	0.1672	0.095	0.2034	0.0311	0.049	0.2965	-0.0281	0.2369	17.8719	-1.292	-94.2411
18	1.097	0.1675	-0.659	0.6134	-0.3806	0.531	-0.1115	0.4474	-0.0668	-0.1603	-0.0004	0.0317	0.1293	0.0911	0.0403	0.0867	-0.015	-0.0069	0.2237	0.0293	0.0958	10.5502	1.2855	-90.1862
19	0.7475	0.4041	-0.5125	2.2658	0.4447	1.2114	-0.059	0.3558	-0.6543	-0.2377	0.0816	-0.4262	0.642	0.2784	-0.0721	0.3263	0.0187	0.0635	0.2234	-0.0347	0.3094	9.2137	-9.1958	-88.919

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'B' and (resid 1 through 79 )
2	X-RAY DIFFRACTION	2	chain 'B' and (resid 80 through 111 )
3	X-RAY DIFFRACTION	3	chain 'B' and (resid 112 through 136 )
4	X-RAY DIFFRACTION	4	chain 'B' and (resid 137 through 166 )
5	X-RAY DIFFRACTION	5	chain 'B' and (resid 167 through 192 )
6	X-RAY DIFFRACTION	6	chain 'B' and (resid 193 through 239 )
7	X-RAY DIFFRACTION	7	chain 'B' and (resid 240 through 275 )
8	X-RAY DIFFRACTION	8	chain 'B' and (resid 276 through 307 )
9	X-RAY DIFFRACTION	9	chain 'B' and (resid 308 through 329 )
10	X-RAY DIFFRACTION	10	chain 'B' and (resid 330 through 501 )
11	X-RAY DIFFRACTION	11	chain 'A' and (resid 2 through 34 )
12	X-RAY DIFFRACTION	12	chain 'A' and (resid 35 through 127 )
13	X-RAY DIFFRACTION	13	chain 'A' and (resid 128 through 151 )
14	X-RAY DIFFRACTION	14	chain 'A' and (resid 152 through 192 )
15	X-RAY DIFFRACTION	15	chain 'A' and (resid 193 through 239 )
16	X-RAY DIFFRACTION	16	chain 'A' and (resid 240 through 271 )
17	X-RAY DIFFRACTION	17	chain 'A' and (resid 272 through 293 )
18	X-RAY DIFFRACTION	18	chain 'A' and (resid 294 through 342 )
19	X-RAY DIFFRACTION	19	chain 'A' and (resid 343 through 359 )

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