1JJT

IMP-1 METALLO BETA-LACTAMASE FROM PSEUDOMONAS AERUGINOSA IN COMPLEX WITH A BIARYL SUCCINIC ACID INHIBITOR (1)

PDB DOI: https://doi.org/10.2210/pdb1JJT/pdb

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

Deposited: 2001-07-09 Released: 2001-07-25
Deposition Author(s): Fitzgerald, P.M.D., Sharma, N.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free: 0.296
R-Value Observed: 0.199

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Succinic acids as potent inhibitors of plasmid-borne IMP-1 metallo-beta-lactamase.

Toney, J.H., Hammond, G.G., Fitzgerald, P.M., Sharma, N., Balkovec, J.M., Rouen, G.P., Olson, S.H., Hammond, M.L., Greenlee, M.L., Gao, Y.D.

(2001) J Biol Chem 276: 31913-31918

PubMed: 11390410 Search on PubMed
DOI: https://doi.org/10.1074/jbc.M104742200
Primary Citation of Related Structures:
1JJE, 1JJT

PubMed Abstract:
IMP-1 metallo-beta-lactamase (class B) is a plasmid-borne zinc metalloenzyme that efficiently hydrolyzes beta-lactam antibiotics, including carbapenems, rendering them ineffective. Because IMP-1 has been found in several clinically important carbapenem-resistant pathogens, there is a need for inhibitors of this enzyme that could protect broad spectrum antibiotics such as imipenem from hydrolysis and thus extend their utility. We have identified a series of 2,3-(S,S)-disubstituted succinic acids that are potent inhibitors of IMP-1. Determination of high resolution crystal structures and molecular modeling of succinic acid inhibitor complexes with IMP-1 has allowed an understanding of the potency, stereochemistry, and structure-activity relationships of these inhibitors.

Organizational Affiliation

Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA. jeff_toney@merck.com

Macromolecule Content

Total Structure Weight: 51.58 kDa
Atom Count: 3,964
Modelled Residue Count: 440
Deposited Residue Count: 456
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
IMP-1 METALLO BETA-LACTAMASE	A, B	228	Pseudomonas aeruginosa	Mutation(s): 0 EC: 3.5.2.6
UniProt
Find proteins for Q79MP6 (Pseudomonas aeruginosa) Explore Q79MP6 Go to UniProtKB: Q79MP6
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q79MP6
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
BDS Query on BDS Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain L [auth B] MOL2 format, chain G [auth A] MOL2 format, chain L [auth B]	G [auth A], L [auth B]	2,3-BIS-BENZO[1,3]DIOXOL-5-YLMETHYL-SUCCINIC ACID C₂₀ H₁₈ O₈ FFYBYVPVYLMLAR-KBPBESRZSA-N		Interactions Focus chain G [auth A] Focus chain L [auth B] Interactions & Density Focus chain G [auth A] Focus chain L [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain F [auth A] SDF format, chain H [auth B] SDF format, chain I [auth B] SDF format, chain K [auth B] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain F [auth A] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B] MOL2 format, chain K [auth B]	C [auth A] D [auth A] F [auth A] H [auth B] I [auth B] C [auth A], D [auth A], F [auth A], H [auth B], I [auth B], K [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain D [auth A] Focus chain F [auth A] Focus chain H [auth B] Focus chain I [auth B] Focus chain K [auth B] Interactions & Density Focus chain C [auth A] Focus chain D [auth A] Focus chain F [auth A] Focus chain H [auth B] Focus chain I [auth B] Focus chain K [auth B]
ACT Query on ACT Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain J [auth B] MOL2 format, chain E [auth A] MOL2 format, chain J [auth B]	E [auth A], J [auth B]	ACETATE ION C₂ H₃ O₂ QTBSBXVTEAMEQO-UHFFFAOYSA-M		Interactions Focus chain E [auth A] Focus chain J [auth B] Interactions & Density Focus chain E [auth A] Focus chain J [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
BDS	Binding MOAD: 1JJT	IC50: 9 (nM) from 1 assay(s)
	PDBBind: 1JJT	IC50: 9 (nM) from 1 assay(s)
	BindingDB: 1JJT	IC50: 9 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free: 0.296
R-Value Observed: 0.199
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 71.8	α = 90
b = 45.18	β = 100.32
c = 64.51	γ = 90

Software Package:

Software Name	Purpose
MERLOT	phasing
SHELXL-97	refinement
X-GEN	data reduction
X-GEN	data scaling

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2001-07-25

Deposition Author(s):

Fitzgerald, P.M.D.

Sharma, N.

Revision History (Full details and data files)

Version 1.0: 2001-07-25
Type: Initial release
Version 1.1: 2008-04-27
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Derived calculations, Version format compliance
Version 1.3: 2024-04-03
Changes: Data collection, Database references, Derived calculations, Refinement description