4F2K

Macrophage Migration Inhibitory Factor covalently complexed with phenethylisothiocyanate

PDB DOI: https://doi.org/10.2210/pdb4F2K/pdb

Classification: ISOMERASE/ISOMERASE INHIBITOR
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2012-05-08 Released: 2012-06-06
Deposition Author(s): Tyndall, J.D.A., Bernhagen, J., Hampton, M.B., Wilbanks, S.M., Rutledge, M.T.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.53 Å
R-Value Free: 0.228
R-Value Work: 0.188
R-Value Observed: 0.190

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

Macrophage migration inhibitory factor covalently complexed with phenethyl isothiocyanate

Tyndall, J.D.A., Lue, H., Rutledge, M.T., Bernhagen, J., Hampton, M.B., Wilbanks, S.M.

(2012) Acta Crystallogr Sect F Struct Biol Cryst Commun 68: 999-1002

PubMed: 22949182 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1107/S1744309112030552
Primary Citation of Related Structures:
4F2K

PubMed Abstract:
Macrophage migration inhibitory factor is irreversibly inhibited via covalent modification by phenethyl isothiocyanate, a naturally occurring compound with anti-inflammatory and anticancer properties. The structure of the modified protein obtained from X-ray diffraction data to 1.64 Å resolution is presented. The inhibitor sits within a deep hydrophobic pocket between subunits of the homotrimer and is highly ordered. The secondary structure of macrophage migratory inhibitory factor is unchanged by this modification, but there are significant rearrangements, including of the side-chain position of Tyr37 and the main chain of residues 31-34. These changes may explain the decreased binding of the modified protein to the receptor CD74. Together with the pocket, the areas of conformational change define specific targets for the design of more selective and potent inhibitors as potential therapeutics.

Organizational Affiliation

School of Pharmacy, University of Otago, PO Box 56, Dunedin 9054, New Zealand.

Macromolecule Content

Total Structure Weight: 38.19 kDa
Atom Count: 3,081
Modelled Residue Count: 342
Deposited Residue Count: 342
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Macrophage migration inhibitory factor	A, B, C	114	Homo sapiens	Mutation(s): 0 Gene Names: GLIF, MIF, MMIF EC: 5.3.2.1 (PDB Primary Data), 5.3.3.12 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P14174 (Homo sapiens) Explore P14174 Go to UniProtKB: P14174
PHAROS: P14174 GTEx: ENSG00000240972
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P14174
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
LE2 Query on LE2 Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain G [auth B] SDF format, chain K [auth C] MOL2 format, chain D [auth A] MOL2 format, chain G [auth B] MOL2 format, chain K [auth C] mmCIF format, chain D [auth A] mmCIF format, chain G [auth B] mmCIF format, chain K [auth C]	D [auth A], G [auth B], K [auth C]	N-(2-phenylethyl)thioformamide C₉ H₁₁ N S WVJCPUDEWCGDGL-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain G [auth B] Focus chain K [auth C] Interactions & Density Focus chain D [auth A] Focus chain G [auth B] Focus chain K [auth C]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain H [auth B] SDF format, chain L [auth C] SDF format, chain M [auth C] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] MOL2 format, chain L [auth C] MOL2 format, chain M [auth C] mmCIF format, chain E [auth A] mmCIF format, chain H [auth B] mmCIF format, chain L [auth C] mmCIF format, chain M [auth C]	E [auth A], H [auth B], L [auth C], M [auth C]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain E [auth A] Focus chain H [auth B] Focus chain L [auth C] Focus chain M [auth C] Interactions & Density Focus chain E [auth A] Focus chain H [auth B] Focus chain L [auth C] Focus chain M [auth C]
IPA Query on IPA Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain I [auth B] SDF format, chain J [auth B] SDF format, chain N [auth C] MOL2 format, chain F [auth A] MOL2 format, chain I [auth B] MOL2 format, chain J [auth B] MOL2 format, chain N [auth C] mmCIF format, chain F [auth A] mmCIF format, chain I [auth B] mmCIF format, chain J [auth B] mmCIF format, chain N [auth C]	F [auth A], I [auth B], J [auth B], N [auth C]	ISOPROPYL ALCOHOL C₃ H₈ O KFZMGEQAYNKOFK-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain I [auth B] Focus chain J [auth B] Focus chain N [auth C] Interactions & Density Focus chain F [auth A] Focus chain I [auth B] Focus chain J [auth B] Focus chain N [auth C]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.53 Å
R-Value Free: 0.228
R-Value Work: 0.188
R-Value Observed: 0.190
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 67.728	α = 90
b = 68.245	β = 90
c = 88.715	γ = 90

Software Package:

Software Name	Purpose
PHASER	phasing
REFMAC	refinement
PDB_EXTRACT	data extraction
CrystalClear	data collection
CrystalClear	data reduction
CrystalClear	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2012-06-06

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2012-06-06
Type: Initial release
Version 1.1: 2012-12-26
Changes: Database references
Version 1.2: 2023-11-08
Changes: Data collection, Database references, Derived calculations, Refinement description
Version 1.3: 2024-11-20
Changes: Structure summary