5HVH

Crystal Structure of Thrombin-activatable Fibrinolysis Inhibitor in Complex with two Inhibitory Nanobodies

PDB DOI: https://doi.org/10.2210/pdb5HVH/pdb

Classification: HYDROLASE/HYDROLASE INHIBITOR
Organism(s): Homo sapiens, Vicugna pacos
Expression System: Komagataella pastoris, Escherichia coli
Mutation(s): Yes

Deposited: 2016-01-28 Released: 2016-06-22
Deposition Author(s): Zhou, X., Weeks, S.D., Strelkov, S.V., Declerck, P.J.
Funding Organization(s): FWO-Vlaanderen

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.00 Å
R-Value Free: 0.202
R-Value Work: 0.190
R-Value Observed: 0.190

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Elucidation of the molecular mechanisms of two nanobodies that inhibit thrombin-activatable fibrinolysis inhibitor activation and activated thrombin-activatable fibrinolysis inhibitor activity.

Zhou, X., Weeks, S.D., Ameloot, P., Callewaert, N., Strelkov, S.V., Declerck, P.J.

(2016) J Thromb Haemost 14: 1629-1638

PubMed: 27279497 Search on PubMed
DOI: https://doi.org/10.1111/jth.13381
Primary Citation of Related Structures:
5HVF, 5HVG, 5HVH

PubMed Abstract:
Essentials Thrombin-activatable fibrinolysis inhibitor (TAFI) is a risk factor for cardiovascular disorders. TAFI inhibitory nanobodies represent a promising step in developing profibrinolytic therapeutics. We have solved three crystal structures of TAFI in complex with inhibitory nanobodies. Nanobodies inhibit TAFI through distinct mechanisms and represent novel profibrinolytic leads.

Organizational Affiliation

Department of Pharmaceutical and Pharmacologic Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven, Belgium.

Macromolecule Content

Total Structure Weight: 75.38 kDa
Atom Count: 5,160
Modelled Residue Count: 639
Deposited Residue Count: 654
Unique protein chains: 3

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Carboxypeptidase B2	A	401	Homo sapiens	Mutation(s): 4 Gene Names: CPB2 EC: 3.4.17.20
UniProt & NIH Common Fund Data Resources
Find proteins for Q96IY4 (Homo sapiens) Explore Q96IY4 Go to UniProtKB: Q96IY4
PHAROS: Q96IY4 GTEx: ENSG00000080618
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q96IY4
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
VHH-a204	B	128	Vicugna pacos	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
VHH-i83	C	125	Vicugna pacos	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Oligosaccharides

Help

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

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NAG Query on NAG Download Ideal Coordinates CCD File SDF format, chain G [auth A] MOL2 format, chain G [auth A]	G [auth A]	2-acetamido-2-deoxy-beta-D-glucopyranose C₈ H₁₅ N O₆ OVRNDRQMDRJTHS-FMDGEEDCSA-N		Interactions Focus chain G [auth A] Interactions & Density Focus chain G [auth A]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain H [auth A] MOL2 format, chain H [auth A]	H [auth A]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain H [auth A] Interactions & Density Focus chain H [auth A]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 3.00 Å
R-Value Free: 0.202
R-Value Work: 0.190
R-Value Observed: 0.190
Space Group: P 6₂ 2 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 196.986	α = 90
b = 196.986	β = 90
c = 147.512	γ = 120

Software Package:

Software Name	Purpose
BUSTER-TNT	refinement
Aimless	data scaling
PHASER	phasing
PDB_EXTRACT	data extraction
XDS	data reduction

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2016-06-22

Deposition Author(s):

Funding Organization	Location	Grant Number
FWO-Vlaanderen	Belgium	G072915N

Revision History (Full details and data files)

Version 1.0: 2016-06-22
Type: Initial release
Version 1.1: 2016-08-03
Changes: Database references
Version 1.2: 2016-08-31
Changes: Database references
Version 2.0: 2020-07-29
Type: Remediation
Reason: Carbohydrate remediation
Changes: Atomic model, Data collection, Derived calculations, Structure summary
Version 2.1: 2024-01-10
Changes: Data collection, Database references, Refinement description, Structure summary