1MZC

Co-Crystal Structure Of Human Farnesyltransferase With Farnesyldiphosphate and Inhibitor Compound 33a


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.177 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Dual Protein Farnesyltransferase-Geranylgeranyltransferase-I Inhibitors as Potential Cancer Chemotherapeutic Agents.

DeSolms, S.J.Ciccarone, T.M.MacTough, S.C.Shaw, A.W.Buser, C.A.Ellis-Hutchings, M.Fernandes, C.Hamilton, K.A.Huber, H.E.Kohl, N.E.Lobell, R.B.Robinson, R.G.Tsou, N.N.Walsh, E.S.Graham, S.L.Beese, L.S.Taylor, J.S.

(2003) J Med Chem 46: 2973-2984

  • DOI: https://doi.org/10.1021/jm020587n
  • Primary Citation of Related Structures:  
    1MZC

  • PubMed Abstract: 

    A series of novel diaryl ether lactams have been identified as very potent dual inhibitors of protein farnesyltransferase (FTase) and protein geranylgeranyltransferase I (GGTase-I), enzymes involved in the prenylation of Ras. The structure of the complex formed between one of these compounds and FTase has been determined by X-ray crystallography. These compounds are the first reported to inhibit the prenylation of the important oncogene Ki-Ras4B in vivo. Unfortunately, doses sufficient to achieve this endpoint were rapidly lethal.


  • Organizational Affiliation

    Departments of Medicinal Chemistry and Cancer Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein Farnesyltransferase alpha Subunit382Homo sapiensMutation(s): 0 
EC: 2.5.1
UniProt & NIH Common Fund Data Resources
Find proteins for P49354 (Homo sapiens)
Explore P49354 
Go to UniProtKB:  P49354
PHAROS:  P49354
GTEx:  ENSG00000168522 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP49354
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Protein Farnesyltransferase beta Subunit437Homo sapiensMutation(s): 0 
EC: 2.5.1
UniProt & NIH Common Fund Data Resources
Find proteins for P49356 (Homo sapiens)
Explore P49356 
Go to UniProtKB:  P49356
PHAROS:  P49356
GTEx:  ENSG00000257365 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP49356
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-fructofuranose-(2-1)-alpha-D-glucopyranose
C
2N/A
Glycosylation Resources
GlyTouCan:  G05551OP
GlyCosmos:  G05551OP
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
BNE
Query on BNE

Download Ideal Coordinates CCD File 
F [auth B]2-[3-(3-ETHYL-1-METHYL-2-OXO-AZEPAN-3-YL)-PHENOXY]-4-[1-AMINO-1-(1-METHYL-1H-IMIDIZOL-5-YL)-ETHYL]-BENZONITRILE
C28 H33 N5 O2
MHNMEERHZSPWFL-NSOVKSMOSA-N
FPP
Query on FPP

Download Ideal Coordinates CCD File 
E [auth B]FARNESYL DIPHOSPHATE
C15 H28 O7 P2
VWFJDQUYCIWHTN-YFVJMOTDSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
D [auth B]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
FPP BindingDB:  1MZC Kd: 2 (nM) from 1 assay(s)
BNE BindingDB:  1MZC IC50: min: 0.06, max: 5.1 (nM) from 4 assay(s)
EC50: 470 (nM) from 1 assay(s)
Binding MOAD:  1MZC IC50: 0.06 (nM) from 1 assay(s)
PDBBind:  1MZC IC50: 0.06 (nM) from 1 assay(s)
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.177 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 178.385α = 90
b = 178.385β = 90
c = 64.579γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2003-07-08
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Structure summary
  • Version 2.1: 2024-02-14
    Changes: Data collection, Database references, Refinement description, Structure summary