1MCJ

PRINCIPLES AND PITFALLS IN DESIGNING SITE DIRECTED PEPTIDE LIGANDS


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Observed: 0.193 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Principles and pitfalls in designing site-directed peptide ligands.

Edmundson, A.B.Harris, D.L.Fan, Z.C.Guddat, L.W.Schley, B.T.Hanson, B.L.Tribbick, G.Geysen, H.M.

(1993) Proteins 16: 246-267

  • DOI: https://doi.org/10.1002/prot.340160304
  • Primary Citation of Related Structures:  
    1MCB, 1MCC, 1MCD, 1MCE, 1MCF, 1MCH, 1MCI, 1MCJ, 1MCK, 1MCL, 1MCN, 1MCQ, 1MCR, 1MCS

  • PubMed Abstract: 

    An immunoglobulin light chain dimer with a large generic binding cavity was used as a host molecule for designing a series of peptide guest ligands. In a screening procedure peptides coupled to solid supports were systematically tested for binding activity by enzyme linked immunosorbent assays (ELISA). Key members of the binding series were synthesized in milligram quantities and diffused into crystals of the host molecule for X-ray analyses. These peptides were incrementally increased in size and affinity until they nearly filled the cavity. Progressive changes in binding patterns were mapped by comparisons of crystallographically refined structures of 14 peptide-protein complexes at 2.7 A resolution. These comparisons led to guidelines for ligand design and also suggested ways to modify previously established binding patterns. By manipulating equilibria involving histidine, for example, it was possible to abolish one important intramolecular interaction of the bound ligand and substitute another. These events triggered a change in conformation of the ligand from a compact to an extended form and a comprehensive change in the mode of binding to the protein. In dipeptides of histidine and proline, protonation of both imidazolium nitrogen atoms was used to program an end-to-end reversal of the direction in which the ligand was inserted into the binding cavity. Peptides cocrystallized with proteins produced complexes somewhat different in structure from those in which ligands were diffused into preexisting crystals. In such a large and malleable cavity, space utilization was thus different when a ligand was introduced before the imposition of crystal packing restraints.


  • Organizational Affiliation

    Harrington Cancer Center, Amarillo, Texas 79106.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
IMMUNOGLOBULIN LAMBDA DIMER MCG (LIGHT CHAIN)
A, B
216Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
PEPTIDE N-ACETYL-D-PHE-L-HIS-D-PRO-NH2C [auth P]5N/AMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DPN
Query on DPN

Download Ideal Coordinates CCD File 
E [auth P]D-PHENYLALANINE
C9 H11 N O2
COLNVLDHVKWLRT-MRVPVSSYSA-N
DPR
Query on DPR

Download Ideal Coordinates CCD File 
F [auth P]D-PROLINE
C5 H9 N O2
ONIBWKKTOPOVIA-SCSAIBSYSA-N
ACE
Query on ACE

Download Ideal Coordinates CCD File 
D [auth A]ACETYL GROUP
C2 H4 O
IKHGUXGNUITLKF-UHFFFAOYSA-N
NH2
Query on NH2

Download Ideal Coordinates CCD File 
G [auth P]AMINO GROUP
H2 N
QGZKDVFQNNGYKY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Observed: 0.193 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.3α = 90
b = 72.3β = 90
c = 185.9γ = 120
Software Package:
Software NamePurpose
X-PLORmodel building
PROLSQrefinement
X-PLORrefinement
X-PLORphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1994-01-31
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-11-29
    Changes: Derived calculations, Other