5ACM

Mcg immunoglobulin variable domain with methylene blue

PDB DOI: https://doi.org/10.2210/pdb5ACM/pdb

Classification: IMMUNE SYSTEM
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2015-08-17 Released: 2015-12-02
Deposition Author(s): Brumshtein, B., Esswein, S.R., Salwinski, L., Phillips, M.L., Ly, A.T., Cascio, D., Sawaya, M.R., Eisenberg, D.S.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.05 Å
R-Value Free: 0.122
R-Value Work: 0.110
R-Value Observed: 0.111

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

Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain.

Brumshtein, B., Esswein, S.R., Salwinski, L., Phillips, M.L., Ly, A.T., Cascio, D., Sawaya, M.R., Eisenberg, D.S.

(2015) Elife 4: e10935-e10935

PubMed: 26576950 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.7554/eLife.10935
Primary Citation of Related Structures:
5ACL, 5ACM

PubMed Abstract:
Overproduction of immunoglobulin light chains leads to systemic amyloidosis, a lethal disease characterized by the formation of amyloid fibrils in patients' tissues. Excess light chains are in equilibrium between dimers and less stable monomers which can undergo irreversible aggregation to the amyloid state. The dimers therefore must disassociate into monomers prior to forming amyloid fibrils. Here we identify ligands that inhibit amyloid formation by stabilizing the Mcg light chain variable domain dimer and shifting the equilibrium away from the amyloid-prone monomer.

Organizational Affiliation

Department of Biological Chemistry, Howard Hughes Medical Institute, UCLA, Los Angeles, United States.

Macromolecule Content

Total Structure Weight: 24.08 kDa
Atom Count: 1,873
Modelled Residue Count: 218
Deposited Residue Count: 222
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
MCG	A, B	111	Homo sapiens	Mutation(s): 0
UniProt & NIH Common Fund Data Resources
Find proteins for P01709 (Homo sapiens) Explore P01709 Go to UniProtKB: P01709
GTEx: ENSG00000278196
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P01709
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
MBT Query on MBT Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A] mmCIF format, chain C [auth A]	C [auth A]	3,7-BIS(DIMETHYLAMINO)PHENOTHIAZIN-5-IUM C₁₆ H₁₈ N₃ S RBTBFTRPCNLSDE-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain H [auth B] SDF format, chain I [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain H [auth B] mmCIF format, chain I [auth B]	D [auth A] E [auth A] F [auth A] G [auth A] H [auth B] D [auth A], E [auth A], F [auth A], G [auth A], H [auth B], I [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth B] Focus chain I [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain H [auth B] Focus chain I [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain J [auth B] MOL2 format, chain J [auth B] mmCIF format, chain J [auth B]	J [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain J [auth B] Interactions & Density Focus chain J [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.05 Å
R-Value Free: 0.122
R-Value Work: 0.110
R-Value Observed: 0.111
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 39.22	α = 90
b = 31.08	β = 90.09
c = 73.63	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
XDS	data reduction
XSCALE	data scaling
PHASER	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2015-12-02

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2015-12-02
Type: Initial release
Version 1.1: 2017-03-22
Changes: Database references
Version 1.2: 2017-09-13
Changes: Data collection
Version 1.3: 2024-01-10
Changes: Data collection, Database references, Derived calculations, Other, Refinement description

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Deposit Data

Help and Resources

5ACM

Mcg immunoglobulin variable domain with methylene blue

Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain.

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

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Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)