5EIZ

Crystal structure of Y99A mutant of human macrophage migration inhibitory factor

PDB DOI: https://doi.org/10.2210/pdb5EIZ/pdb

Classification: ISOMERASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2015-10-30 Released: 2015-11-11
Deposition Author(s): Pantouris, G., Lolis, E.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.96 Å
R-Value Free: 0.181
R-Value Work: 0.157
R-Value Observed: 0.158

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

This is version 1.2 of the entry. See complete history.

Literature

Nanosecond Dynamics Regulate the MIF-Induced Activity of CD74.

Pantouris, G., Ho, J., Shah, D., Syed, M.A., Leng, L., Bhandari, V., Bucala, R., Batista, V.S., Loria, J.P., Lolis, E.J.

(2018) Angew Chem Int Ed Engl

PubMed: 29669180 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1002/anie.201803191
Primary Citation of Related Structures:
5EIZ, 5UZY, 6BG6, 6BG7

PubMed Abstract:
Macrophage migration inhibitory factor (MIF) activates CD74, which leads to severe disorders including inflammation, autoimmune diseases and cancer under pathological conditions. Molecular dynamics (MD) simulations up to one microsecond revealed dynamical correlation between a residue located at the opening of one end of the MIF solvent channel, previously thought to be a consequence of homotrimerization, and residues in a distal region responsible for CD74 activation. Experiments verified the allosteric regulatory site and identified a pathway to this site via the MIF β-strands. The reported findings provide fundamental insights on a dynamic mechanism that controls the MIF-induced activation of CD74.

Organizational Affiliation

Department of Pharmacology, School of Medicine, Yale University, New Haven, CT, 06510, USA.

Macromolecule Content

Total Structure Weight: 37.47 kDa
Atom Count: 2,888
Modelled Residue Count: 342
Deposited Residue Count: 342
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(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): 1 Gene Names: MIF, GLIF, 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
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain H [auth B] SDF format, chain K [auth C] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] MOL2 format, chain K [auth C] mmCIF format, chain E [auth A] mmCIF format, chain H [auth B] mmCIF format, chain K [auth C]	E [auth A], H [auth B], K [auth C]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain E [auth A] Focus chain H [auth B] Focus chain K [auth C] Interactions & Density Focus chain E [auth A] Focus chain H [auth B] Focus chain K [auth C]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain G [auth B] SDF format, chain J [auth C] MOL2 format, chain D [auth A] MOL2 format, chain G [auth B] MOL2 format, chain J [auth C] mmCIF format, chain D [auth A] mmCIF format, chain G [auth B] mmCIF format, chain J [auth C]	D [auth A], G [auth B], J [auth C]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Focus chain G [auth B] Focus chain J [auth C] Interactions & Density Focus chain D [auth A] Focus chain G [auth B] Focus chain J [auth C]
IPA Query on IPA Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain I [auth B] MOL2 format, chain F [auth A] MOL2 format, chain I [auth B] mmCIF format, chain F [auth A] mmCIF format, chain I [auth B]	F [auth A], I [auth B]	ISOPROPYL ALCOHOL C₃ H₈ O KFZMGEQAYNKOFK-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain I [auth B] Interactions & Density Focus chain F [auth A] Focus chain I [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.96 Å
R-Value Free: 0.181
R-Value Work: 0.157
R-Value Observed: 0.158
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 67.696	α = 90
b = 67.958	β = 90
c = 86.519	γ = 90

Software Package:

Software Name	Purpose
HKL-2000	data collection
HKL-2000	data scaling
REFMAC	refinement
PDB_EXTRACT	data extraction
DENZO	data reduction
PHASER	phasing

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2015-11-11

Deposition Author(s):

Pantouris, G.

Lolis, E.

Revision History (Full details and data files)

Version 1.0: 2015-11-11
Type: Initial release
Version 1.1: 2018-06-06
Changes: Data collection, Database references, Derived calculations
Version 1.2: 2023-09-27
Changes: Data collection, Database references, Refinement description