4BDV

CRYSTAL STRUCTURE OF A TRUNCATED B-DOMAIN HUMAN FACTOR VIII

PDB DOI: https://doi.org/10.2210/pdb4BDV/pdb

Classification: BLOOD CLOTTING
Organism(s): Homo sapiens
Expression System: Cricetulus griseus
Mutation(s): No

Deposited: 2012-10-08 Released: 2013-05-15
Deposition Author(s): Svensson, L.A., Thim, L., Olsen, O.H., Nicolaisen, E.M.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.98 Å
R-Value Free: 0.246
R-Value Work: 0.162
R-Value Observed: 0.166

wwPDB Validation 3D Report Full Report

This is version 2.1 of the entry. See complete history.

Literature

Evaluation of the Metal Binding Sites in a Recombinant Coagulation Factor Viii Identifies Two Sites with Unique Metal Binding Properties.

Svensson, L.A., Thim, L., Olsen, O.H., Nicolaisen, E.M.

(2013) Biol Chem 394: 761

PubMed: 23435097 Search on PubMed
DOI: https://doi.org/10.1515/hsz-2012-0298
Primary Citation of Related Structures:
4BDV

PubMed Abstract:
Coagulation factor VIII is a glycosylated, non-covalent heterodimer consisting of a heavy chain (A1-A2-B domains) and a light chain (A3-C1-C2 domains). The association of the chains, and the stability and function of the dimer depend on the presence of metal ions. We applied X-ray fluorescence, X-ray crystallographic structure determination with anomalous signals at different wavelengths, and colorimetric measurements to evaluate the metal binding sites in a recombinant factor VIII molecule, turoctocog alfa. We identified a metal binding site in domain A3 dominated by Cu(+) binding and a site in domain A1 dominated by Zn(2+) binding.

Organizational Affiliation

Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark. AnSv@novonordisk.com

Macromolecule Content

Total Structure Weight: 167.98 kDa
Atom Count: 9,973
Modelled Residue Count: 1,218
Deposited Residue Count: 1,445
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
FACTOR VIIIA HEAVY CHAIN, 92 KDA ISOFORM, B DOMAIN	A	760	Homo sapiens	Mutation(s): 0
UniProt & NIH Common Fund Data Resources
Find proteins for P00451 (Homo sapiens) Explore P00451 Go to UniProtKB: P00451
PHAROS: P00451 GTEx: ENSG00000185010
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P00451
Sequence Annotations Expand
Reference Sequence

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(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
FACTOR VIIIA LIGHT CHAIN	B	685	Homo sapiens	Mutation(s): 0
UniProt & NIH Common Fund Data Resources
Find proteins for P00451 (Homo sapiens) Explore P00451 Go to UniProtKB: P00451
PHAROS: P00451 GTEx: ENSG00000185010
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P00451
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

Help

Entity ID: 3
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	C	2		N-Glycosylation	Interactions Focus chain C Interactions & Density Focus chain C
Glycosylation Resources
GlyTouCan: G42666HT GlyCosmos: G42666HT GlyGen: G42666HT

Entity ID: 4
Molecule	Chains	Length	2D Diagram	Glycosylation	3D Interactions
beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose	D	5		N-Glycosylation	Interactions Focus chain D Interactions & Density Focus chain D
Glycosylation Resources
GlyTouCan: G89225LT GlyCosmos: G89225LT GlyGen: G89225LT

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A]	E [auth A]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]
CU1 Query on CU1 Download Ideal Coordinates CCD File SDF format, chain H [auth B] MOL2 format, chain H [auth B]	H [auth B]	COPPER (I) ION Cu VMQMZMRVKUZKQL-UHFFFAOYSA-N		Interactions Focus chain H [auth B] Interactions & Density Focus chain H [auth B]
EDO Query on EDO Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain I [auth B] MOL2 format, chain G [auth A] MOL2 format, chain I [auth B]	G [auth A], I [auth B]	1,2-ETHANEDIOL C₂ H₆ O₂ LYCAIKOWRPUZTN-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Focus chain I [auth B] Interactions & Density Focus chain G [auth A] Focus chain I [auth B]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain F [auth A] MOL2 format, chain F [auth A]	F [auth A]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Interactions & Density Focus chain F [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 3.98 Å
R-Value Free: 0.246
R-Value Work: 0.162
R-Value Observed: 0.166
Space Group: P 4₁ 2₁ 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 133.84	α = 90
b = 133.84	β = 90
c = 355.81	γ = 90

Software Package:

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

Structure Validation

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Entry History

Deposition Data

Released Date: 2013-05-15

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2013-05-15
Type: Initial release
Version 1.1: 2017-01-25
Changes: Data collection
Version 1.2: 2018-01-17
Changes: Data collection
Version 2.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Advisory, Atomic model, Data collection, Derived calculations, Other, Structure summary
Version 2.1: 2023-12-20
Changes: Data collection, Database references, Refinement description, Structure summary