2ZIS | pdb_00002zis

Crystal Structure of rat protein farnesyltransferase complexed with a bezoruran inhibitor and FPP

PDB DOI: https://doi.org/10.2210/pdb2ZIS/pdb

Classification: TRANSFERASE
Organism(s): Rattus norvegicus
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2008-02-22 Released: 2009-02-24
Deposition Author(s): Fukami, T.A., Sogabe, S., Nagata, Y., Kondoh, O., Ishii, N.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free:
0.222 (Depositor), 0.180 (DCC)
R-Value Work:
0.184 (Depositor), 0.180 (DCC)

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Synthesis and structure-activity relationships of novel benzofuran farnesyltransferase inhibitors

Asoh, K., Kohchi, M., Hyoudoh, I., Ohtsuka, T., Masubuchi, M., Kawasaki, K., Ebiike, H., Shiratori, Y., Fukami, T.A., Kondoh, O., Tsukaguchi, T., Ishii, N., Aoki, Y., Shimma, N., Sakaitani, M.

(2009) Bioorg Med Chem Lett 19: 1753-1757

PubMed: 19217288 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2009.01.074
Primary Citation of Related Structures:
2ZIR, 2ZIS

PubMed Abstract:
A series of benzofuran-based farnesyltransferase inhibitors have been designed and synthesized as antitumor agents. Among them, 11f showed the most potent enzyme inhibitory activity (IC(50)=1.1nM) and antitumor activity in human cancer xenografts in mice.

Organizational Affiliation

Kamakura Research Laboratories, Chugai Pharmaceutical Co. Ltd., 200-Kajiwara, Kamakura, Kanagawa 247-8530, Japan.

Macromolecule Content

Total Structure Weight: 94.41 kDa
Atom Count: 6,315
Modelled Residue Count: 715
Deposited Residue Count: 817
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Protein farnesyltransferase subunit alpha	A	377	Rattus norvegicus	Mutation(s): 1 Gene Names: Fnta EC: 2.5.1.58 (PDB Primary Data), 2.5.1.59 (UniProt)
UniProt
Find proteins for Q04631 (Rattus norvegicus) Explore Q04631 Go to UniProtKB: Q04631
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q04631
Sequence Annotations Expand
Reference Sequence LOADING

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Protein farnesyltransferase subunit beta	B	440	Rattus norvegicus	Mutation(s): 0 Gene Names: Fntb EC: 2.5.1.58
UniProt
Find proteins for Q02293 (Rattus norvegicus) Explore Q02293 Go to UniProtKB: Q02293
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q02293
Sequence Annotations Expand
Reference Sequence LOADING

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NH8 Query on NH8 Download Ideal Coordinates CCD File SDF format, chain F [auth B] MOL2 format, chain F [auth B] mmCIF format, chain F [auth B]	F [auth B]	3-{2-[(S)-(4-cyanophenyl)(hydroxy)(1-methyl-1H-imidazol-5-yl)methyl]-5-nitro-1-benzofuran-7-yl}benzonitrile C₂₇ H₁₇ N₅ O₄ NYEPLLLECMESPU-MHZLTWQESA-N		Interactions Focus chain F [auth B] Interactions & Density Focus chain F [auth B]
FPP Query on FPP Download Ideal Coordinates CCD File SDF format, chain E [auth B] MOL2 format, chain E [auth B] mmCIF format, chain E [auth B]	E [auth B]	FARNESYL DIPHOSPHATE C₁₅ H₂₈ O₇ P₂ VWFJDQUYCIWHTN-YFVJMOTDSA-N		Interactions Focus chain E [auth B] Interactions & Density Focus chain E [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain H [auth B] SDF format, chain I [auth B] SDF format, chain J [auth B] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B] MOL2 format, chain J [auth B] mmCIF format, chain H [auth B] mmCIF format, chain I [auth B] mmCIF format, chain J [auth B]	H [auth B], I [auth B], J [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain H [auth B] Focus chain I [auth B] Focus chain J [auth B] Interactions & Density Focus chain H [auth B] Focus chain I [auth B] Focus chain J [auth B]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain D [auth B] MOL2 format, chain D [auth B] mmCIF format, chain D [auth B]	D [auth B]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain D [auth B] Interactions & Density Focus chain D [auth B]
ACY Query on ACY Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain G [auth B] MOL2 format, chain C [auth A] MOL2 format, chain G [auth B] mmCIF format, chain C [auth A] mmCIF format, chain G [auth B]	C [auth A], G [auth B]	ACETIC ACID C₂ H₄ O₂ QTBSBXVTEAMEQO-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Focus chain G [auth B] Interactions & Density Focus chain C [auth A] Focus chain G [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
FPP	BindingDB: 2ZIS	Kd: 2 (nM) from 1 assay(s)
NH8	BindingDB: 2ZIS	IC50: 2.8 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.222 (Depositor), 0.180 (DCC)
R-Value Work: 0.184 (Depositor), 0.180 (DCC)

Space Group: P 6₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 171.826	α = 90
b = 171.826	β = 90
c = 69.063	γ = 120

Software Package:

Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
MOLREP	phasing
CNX	refinement
PDB_EXTRACT	data extraction

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2009-02-24

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2009-02-24
Type: Initial release
Version 1.1: 2011-07-13
Changes: Non-polymer description, Version format compliance
Version 1.2: 2021-11-10
Changes: Database references, Derived calculations
Version 1.3: 2023-11-01
Changes: Data collection, Refinement description