6QF9

Structure of an anti-Mcl1 scFv


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.43 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.186 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Antibody fragments structurally enable a drug-discovery campaign on the cancer target Mcl-1.

Luptak, J.Bista, M.Fisher, D.Flavell, L.Gao, N.Wickson, K.Kazmirski, S.L.Howard, T.Rawlins, P.B.Hargreaves, D.

(2019) Acta Crystallogr D Struct Biol 75: 1003-1014

  • DOI: https://doi.org/10.1107/S2059798319014116
  • Primary Citation of Related Structures:  
    6QB3, 6QB4, 6QB6, 6QB9, 6QBC, 6QF9, 6QFC

  • PubMed Abstract: 

    Apoptosis is a crucial process by which multicellular organisms control tissue growth, removal and inflammation. Disruption of the normal apoptotic function is often observed in cancer, where cell death is avoided by the overexpression of anti-apoptotic proteins of the Bcl-2 (B-cell lymphoma 2) family, including Mcl-1 (myeloid cell leukaemia 1). This makes Mcl-1 a potential target for drug therapy, through which normal apoptosis may be restored by inhibiting the protective function of Mcl-1. Here, the discovery and biophysical properties of an anti-Mcl-1 antibody fragment are described and the utility of both the scFv and Fab are demonstrated in generating an Mcl-1 crystal system amenable to iterative structure-guided drug design.


  • Organizational Affiliation

    Discovery Sciences, R&D Biopharmaceuticals, AstraZeneca, Cambridge CB4 0WG, England.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
scFv
A, B
255Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.43 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.186 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 54.165α = 90
b = 62.749β = 105.52
c = 70.557γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
Aimlessdata scaling
BUSTERrefinement
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

  • Released Date: 2019-11-06 
  • Deposition Author(s): Luptak, J.

Revision History  (Full details and data files)

  • Version 1.0: 2019-11-06
    Type: Initial release
  • Version 1.1: 2019-11-13
    Changes: Database references