1LEV

PORCINE KIDNEY FRUCTOSE-1,6-BISPHOSPHATASE COMPLEXED WITH AN AMP-SITE INHIBITOR

PDB DOI: https://doi.org/10.2210/pdb1LEV/pdb

Classification: HYDROLASE
Organism(s): Sus scrofa
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2002-04-10 Released: 2002-10-16
Deposition Author(s): Wright, S.W., Carlo, A.A., Danley, D.E., Hageman, D.L., Karam, G.A., Mansour, M.N., McClure, L.D., Pandit, J., Schulte, G.K., Treadway, J.L., Wang, I.-K., Bauer, P.H.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.15 Å
R-Value Free: 0.255
R-Value Work: 0.193
R-Value Observed: 0.196

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.5 of the entry. See complete history.

Literature

3-(2-carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid: an allosteric inhibitor of fructose-1,6-bisphosphatase at the AMP site.

Wright, S.W., Carlo, A.A., Danley, D.E., Hageman, D.L., Karam, G.A., Mansour, M.N., McClure, L.D., Pandit, J., Schulte, G.K., Treadway, J.L., Wang, I.-K., Bauer, P.H.

(2003) Bioorg Med Chem Lett 13: 2055-2058

PubMed: 12781194 Search on PubMed
DOI: https://doi.org/10.1016/s0960-894x(03)00310-x
Primary Citation of Related Structures:
1LEV

PubMed Abstract:
3-(2-Carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid (MDL-29951), an antagonist of the glycine site of the NMDA receptor, has been found to be an allosteric inhibitor of the enzyme fructose 1,6-bisphosphatase. The compound binds at the AMP regulatory site by X-ray crystallography. This represents a new approach to inhibition of fructose 1,6-bisphosphatase and serves as a lead for further drug design.

Organizational Affiliation

Pfizer Central Research, Eastern Point Road, Box 8220-3141, Groton, CT 06340, USA. [email protected]

Macromolecule Content

Total Structure Weight: 74.75 kDa
Atom Count: 4,947
Modelled Residue Count: 622
Deposited Residue Count: 674
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Fructose-1,6-bisphosphatase	A, B [auth F]	337	Sus scrofa	Mutation(s): 0 EC: 3.1.3.11
UniProt
Find proteins for P00636 (Sus scrofa) Explore P00636 Go to UniProtKB: P00636
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P00636
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
CLI Query on CLI Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain J [auth F] MOL2 format, chain F [auth A] MOL2 format, chain J [auth F] mmCIF format, chain F [auth A] mmCIF format, chain J [auth F]	F [auth A], J [auth F]	3-(2-CARBOXY-ETHYL)-4,6-DICHLORO-1H-INDOLE-2-CARBOXYLIC ACID C₁₂ H₉ Cl₂ N O₄ KNBSYZNKEAWABY-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain J [auth F] Interactions & Density Focus chain F [auth A] Focus chain J [auth F]
F6P Query on F6P Download Ideal Coordinates CCD File SDF format, chain G [auth F] SDF format, chain C [auth A] MOL2 format, chain G [auth F] MOL2 format, chain C [auth A] mmCIF format, chain G [auth F] mmCIF format, chain C [auth A]	C [auth A], G [auth F]	6-O-phosphono-beta-D-fructofuranose C₆ H₁₃ O₉ P BGWGXPAPYGQALX-ARQDHWQXSA-N		Interactions Focus chain C [auth A] Focus chain G [auth F] Interactions & Density Focus chain C [auth A] Focus chain G [auth F]
MN Query on MN Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain H [auth F] SDF format, chain I [auth F] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain H [auth F] MOL2 format, chain I [auth F] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain H [auth F] mmCIF format, chain I [auth F]	D [auth A], E [auth A], H [auth F], I [auth F]	MANGANESE (II) ION Mn WAEMQWOKJMHJLA-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain H [auth F] Focus chain I [auth F] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain H [auth F] Focus chain I [auth F]

Binding Affinity Annotations
ID	Source	Binding Affinity
CLI	BindingDB: 1LEV	IC50: min: 1000, max: 2500 (nM) from 3 assay(s)
CLI	PDBBind: 1LEV	IC50: 2500 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.15 Å
R-Value Free: 0.255
R-Value Work: 0.193
R-Value Observed: 0.196
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 118.87	α = 90
b = 73.446	β = 106.3
c = 78.025	γ = 90

Software Package:

Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
AMoRE	phasing
REFMAC	refinement

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2002-10-16

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2002-10-16
Type: Initial release
Version 1.1: 2008-04-28
Changes: Version format compliance
Version 1.2: 2011-07-13
Changes: Derived calculations, Version format compliance
Version 1.3: 2018-10-03
Changes: Advisory, Data collection
Version 1.4: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Data collection, Database references, Derived calculations, Structure summary
Version 1.5: 2023-08-16
Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description, Structure summary