7E9A

Crystal structure of KPC-2 in complex with (S)-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acrylic acid (4a-(S))

PDB DOI: https://doi.org/10.2210/pdb7E9A/pdb

Classification: HYDROLASE
Organism(s): Klebsiella pneumoniae
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2021-03-03 Released: 2021-08-04
Deposition Author(s): Li, G.-B., Yan, Y.-H.
Funding Organization(s): National Natural Science Foundation of China (NSFC)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.25 Å
R-Value Free: 0.221
R-Value Work: 0.180
R-Value Observed: 0.182

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Design and enantioselective synthesis of 3-( alpha-acrylic acid) benzoxaboroles to combat carbapenemase resistance.

Xiao, Y.C., Chen, X.P., Deng, J., Yan, Y.H., Zhu, K.R., Li, G., Yu, J.L., Brem, J., Chen, F., Schofield, C.J., Li, G.B.

(2021) Chem Commun (Camb) 57: 7709-7712

PubMed: 34259249 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1039/d1cc03026d
Primary Citation of Related Structures:
7E9A

PubMed Abstract:
Chiral 3-substituted benzoxaboroles were designed as carbapenemase inhibitors and efficiently synthesised via asymmetric Morita-Baylis-Hillman reaction. Some of the benzoxaboroles were potent inhibitors of clinically relevant carbapenemases and restored the activity of meropenem in bacteria harbouring these enzymes. Crystallographic analyses validate the proposed mechanism of binding to carbapenemases, i.e. in a manner relating to their antibiotic substrates. The results illustrate how combining a structure-based design approach with asymmetric catalysis can efficiently lead to potent β-lactamase inhibitors and provide a starting point to develop drugs combatting carbapenemases.

Organizational Affiliation

Key Laboratory of Drug-Targeting and Drug Delivery System of the Ministry of Education and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. [email protected].

Macromolecule Content

Total Structure Weight: 114.93 kDa
Atom Count: 8,391
Modelled Residue Count: 1,055
Deposited Residue Count: 1,060
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Beta-lactamase	A, B, C, D	265	Klebsiella pneumoniae	Mutation(s): 0 Gene Names: blaKPC2 EC: 3.5.2.6
UniProt
Find proteins for Q9F663 (Klebsiella pneumoniae) Explore Q9F663 Go to UniProtKB: Q9F663
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q9F663
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
J00 (Subject of Investigation/LOI) Query on J00 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain K [auth B] SDF format, chain Q [auth C] SDF format, chain X [auth D] MOL2 format, chain E [auth A] MOL2 format, chain K [auth B] MOL2 format, chain Q [auth C] MOL2 format, chain X [auth D] mmCIF format, chain E [auth A] mmCIF format, chain K [auth B] mmCIF format, chain Q [auth C] mmCIF format, chain X [auth D]	E [auth A], K [auth B], Q [auth C], X [auth D]	2-[(3S)-1-oxidanyl-3H-2,1-benzoxaborol-3-yl]prop-2-enoic acid C₁₀ H₉ B O₄ BRBGRVSFRVLGNY-SECBINFHSA-N		Interactions Focus chain E [auth A] Focus chain K [auth B] Focus chain Q [auth C] Focus chain X [auth D] Interactions & Density Focus chain E [auth A] Focus chain K [auth B] Focus chain Q [auth C] Focus chain X [auth D]
PEG Query on PEG Download Ideal Coordinates CCD File SDF format, chain AA [auth D] SDF format, chain G [auth A] SDF format, chain L [auth B] SDF format, chain M [auth B] SDF format, chain N [auth B] SDF format, chain O [auth B] SDF format, chain S [auth C] SDF format, chain T [auth C] SDF format, chain U [auth C] SDF format, chain V [auth C] MOL2 format, chain AA [auth D] MOL2 format, chain G [auth A] MOL2 format, chain L [auth B] MOL2 format, chain M [auth B] MOL2 format, chain N [auth B] MOL2 format, chain O [auth B] MOL2 format, chain S [auth C] MOL2 format, chain T [auth C] MOL2 format, chain U [auth C] MOL2 format, chain V [auth C] mmCIF format, chain AA [auth D] mmCIF format, chain G [auth A] mmCIF format, chain L [auth B] mmCIF format, chain M [auth B] mmCIF format, chain N [auth B] mmCIF format, chain O [auth B] mmCIF format, chain S [auth C] mmCIF format, chain T [auth C] mmCIF format, chain U [auth C] mmCIF format, chain V [auth C]	AA [auth D] G [auth A] L [auth B] M [auth B] N [auth B] AA [auth D], G [auth A], L [auth B], M [auth B], N [auth B], O [auth B], S [auth C], T [auth C], U [auth C], V [auth C]	DI(HYDROXYETHYL)ETHER C₄ H₁₀ O₃ MTHSVFCYNBDYFN-UHFFFAOYSA-N		Interactions Focus chain AA [auth D] Focus chain G [auth A] Focus chain L [auth B] Focus chain M [auth B] Focus chain N [auth B] Focus chain O [auth B] Focus chain S [auth C] Focus chain T [auth C] Focus chain U [auth C] Focus chain V [auth C] Interactions & Density Focus chain AA [auth D] Focus chain G [auth A] Focus chain L [auth B] Focus chain M [auth B] Focus chain N [auth B] Focus chain O [auth B] Focus chain S [auth C] Focus chain T [auth C] Focus chain U [auth C] Focus chain V [auth C]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain P [auth B] SDF format, chain W [auth C] SDF format, chain Z [auth D] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain P [auth B] MOL2 format, chain W [auth C] MOL2 format, chain Z [auth D] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain P [auth B] mmCIF format, chain W [auth C] mmCIF format, chain Z [auth D]	H [auth A] I [auth A] J [auth A] P [auth B] W [auth C] H [auth A], I [auth A], J [auth A], P [auth B], W [auth C], Z [auth D]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain P [auth B] Focus chain W [auth C] Focus chain Z [auth D] Interactions & Density Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain P [auth B] Focus chain W [auth C] Focus chain Z [auth D]
ACY Query on ACY Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain R [auth C] SDF format, chain Y [auth D] MOL2 format, chain F [auth A] MOL2 format, chain R [auth C] MOL2 format, chain Y [auth D] mmCIF format, chain F [auth A] mmCIF format, chain R [auth C] mmCIF format, chain Y [auth D]	F [auth A], R [auth C], Y [auth D]	ACETIC ACID C₂ H₄ O₂ QTBSBXVTEAMEQO-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain R [auth C] Focus chain Y [auth D] Interactions & Density Focus chain F [auth A] Focus chain R [auth C] Focus chain Y [auth D]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.25 Å
R-Value Free: 0.221
R-Value Work: 0.180
R-Value Observed: 0.182
Space Group: P 3 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 165.421	α = 90
b = 165.421	β = 90
c = 94.86	γ = 120

Software Package:

Software Name	Purpose
PHENIX	refinement
HKL-2000	data reduction
SCALEPACK	data scaling
PHASER	phasing
PDB_EXTRACT	data extraction

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2021-08-04

Deposition Author(s):

Li, G.-B.

Yan, Y.-H.

Funding Organization	Location	Grant Number
National Natural Science Foundation of China (NSFC)	China	81874291
National Natural Science Foundation of China (NSFC)	China	81502989
National Natural Science Foundation of China (NSFC)	China	82073698

Revision History (Full details and data files)

Version 1.0: 2021-08-04
Type: Initial release
Version 1.1: 2021-08-11
Changes: Database references
Version 1.2: 2021-08-18
Changes: Database references
Version 1.3: 2023-11-29
Changes: Data collection, Refinement description
Version 1.4: 2024-10-23
Changes: Structure summary

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Help and Resources

7E9A

Crystal structure of KPC-2 in complex with (S)-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acrylic acid (4a-(S))

Design and enantioselective synthesis of 3-( alpha-acrylic acid) benzoxaboroles to combat carbapenemase resistance.

Entity ID: 1

UniProt

Entity Groups

Sequence Annotations

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Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)