2WZX

AMP-C BETA-LACTAMASE (PSEUDOMONAS AERUGINOSA)IN COMPLEX WITH compound M-02

PDB DOI: https://doi.org/10.2210/pdb2WZX/pdb

Classification: HYDROLASE
Organism(s): Pseudomonas aeruginosa
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2009-12-03 Released: 2010-01-12
Deposition Author(s): Fitzgerald, P.M.D., Sharma, N., Lu, J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.40 Å
R-Value Free: 0.198
R-Value Work: 0.182
R-Value Observed: 0.183

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Side Chain Sar of Bicyclic Beta-Lactamase Inhibitors (Blis). 1. Discovery of a Class C Bli for Combination with Imipinem.

Blizzard, T.A., Chen, H., Kim, S., Wu, J., Young, K., Park, Y., Ogawa, A., Raghoobar, S., Painter, R.E., Hairston, N., Lee, S.H., Misura, A., Felcetto, T., Fitzgerald, P.M.D., Sharma, N., Lu, J., Ha, S., Hickey, E., Hermes, J., Hammond, M.L.

(2010) Bioorg Med Chem Lett 20: 918

PubMed: 20044254 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2009.12.069
Primary Citation of Related Structures:
2WZX, 2WZZ

PubMed Abstract:
Bridged monobactam beta-lactamase inhibitors were prepared and evaluated as potential partners for combination with imipenem to overcome class C beta-lactamase mediated resistance. The (S)-azepine analog 2 was found to be effective in both in vitro and in vivo assays and was selected for preclinical development.

Organizational Affiliation

Department of Medicinal Chemistry, Merck Research Labs, Rahway, NJ 07065, USA. tim_blizzard@merck.com

Macromolecule Content

Total Structure Weight: 41.11 kDa
Atom Count: 3,136
Modelled Residue Count: 362
Deposited Residue Count: 371
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
BETA-LACTAMASE	A	371	Pseudomonas aeruginosa	Mutation(s): 0 EC: 3.5.2.6
UniProt
Find proteins for P24735 (Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)) Explore P24735 Go to UniProtKB: P24735
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P24735
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
ZX0 Query on ZX0 Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	(3R)-1-[(4S)-azepan-4-ylcarbamoyl]-3-(sulfoamino)-L-proline C₁₂ H₂₂ N₄ O₆ S WWLDRJMXWRULQB-AEJSXWLSSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A]	C [auth A]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
ZX0	PDBBind: 2WZX	IC50: 1000 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.40 Å
R-Value Free: 0.198
R-Value Work: 0.182
R-Value Observed: 0.183
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 44.759	α = 90
b = 72.135	β = 90
c = 105.933	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
DENZO	data reduction
SCALEPACK	data scaling
HKL-2000	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2010-01-12

Deposition Author(s):

Fitzgerald, P.M.D.

Revision History (Full details and data files)

Version 1.0: 2010-01-12
Type: Initial release
Version 1.1: 2011-05-08
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Version format compliance

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.