4OMC

X-ray structure of human furin in complex with the competitive inhibitor meta-guanidinomethyl-Phac-RVR-Amba

PDB DOI: https://doi.org/10.2210/pdb4OMC/pdb

Classification: HYDROLASE/HYDROLASE INHIBITOR
Organism(s): Homo sapiens
Expression System: Homo sapiens
Mutation(s): No

Deposited: 2014-01-27 Released: 2014-04-09
Deposition Author(s): Dahms, S.O., Than, M.E.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.30 Å
R-Value Free: 0.216
R-Value Work: 0.185

wwPDB Validation 3D Report Full Report

This is version 2.0 of the entry. See complete history.

Literature

X-ray Structures of Human Furin in Complex with Competitive Inhibitors.

Dahms, S.O., Hardes, K., Becker, G.L., Steinmetzer, T., Brandstetter, H., Than, M.E.

(2014) ACS Chem Biol 9: 1113-1118

PubMed: 24666235 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1021/cb500087x
Primary Citation of Related Structures:
4OMC, 4OMD

PubMed Abstract:
Furin inhibitors are promising therapeutics for the treatment of cancer and numerous infections caused by bacteria and viruses, including the highly lethal Bacillus anthracis or the pandemic influenza virus. Development and improvement of inhibitors for pharmacological use require a detailed knowledge of the protease's substrate and inhibitor binding properties. Here we present a novel preparation of human furin and the first crystal structures of this enzyme in complex with noncovalent inhibitors. We show the inhibitor exchange by soaking, allowing the investigation of additional inhibitors and substrate analogues. Thus, our work provides a basis for the rational design of furin inhibitors.

Organizational Affiliation

Protein Crystallography Group, Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI) , Beutenbergstr. 11, 07745 Jena, Germany.

Macromolecule Content

Total Structure Weight: 320.81 kDa
Atom Count: 23,092
Modelled Residue Count: 2,822
Deposited Residue Count: 2,922
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Furin	A, B, C, D, E A, B, C, D, E, F	482	Homo sapiens	Mutation(s): 0 Gene Names: FUR, FURIN, PACE, PCSK3 EC: 3.4.21.75
UniProt & NIH Common Fund Data Resources
Find proteins for P09958 (Homo sapiens) Explore P09958 Go to UniProtKB: P09958
PHAROS: P09958 GTEx: ENSG00000140564
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P09958
Sequence Annotations Expand
Reference Sequence

Find similar proteins by: Sequence | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
meta-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)benzamidine	G [auth H] H [auth I] I [auth J] J [auth K] K [auth L] G [auth H], H [auth I], I [auth J], J [auth K], K [auth L], L [auth N]	5	N/A	Mutation(s): 0
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
FMT Query on FMT Download Ideal Coordinates CCD File SDF format, chain AB [auth F] SDF format, chain BB [auth F] SDF format, chain CA [auth C] SDF format, chain CB [auth F] SDF format, chain DA [auth C] SDF format, chain DB [auth F] SDF format, chain EA [auth C] SDF format, chain FA [auth C] SDF format, chain KA [auth D] SDF format, chain LA [auth D] SDF format, chain M [auth A] SDF format, chain MA [auth D] SDF format, chain N [auth A] SDF format, chain NA [auth D] SDF format, chain O [auth A] SDF format, chain P [auth A] SDF format, chain SA [auth E] SDF format, chain TA [auth E] SDF format, chain U [auth B] SDF format, chain UA [auth E] SDF format, chain V [auth B] SDF format, chain VA [auth E] SDF format, chain W [auth B] SDF format, chain X [auth B] MOL2 format, chain AB [auth F] MOL2 format, chain BB [auth F] MOL2 format, chain CA [auth C] MOL2 format, chain CB [auth F] MOL2 format, chain DA [auth C] MOL2 format, chain DB [auth F] MOL2 format, chain EA [auth C] MOL2 format, chain FA [auth C] MOL2 format, chain KA [auth D] MOL2 format, chain LA [auth D] MOL2 format, chain M [auth A] MOL2 format, chain MA [auth D] MOL2 format, chain N [auth A] MOL2 format, chain NA [auth D] MOL2 format, chain O [auth A] MOL2 format, chain P [auth A] MOL2 format, chain SA [auth E] MOL2 format, chain TA [auth E] MOL2 format, chain U [auth B] MOL2 format, chain UA [auth E] MOL2 format, chain V [auth B] MOL2 format, chain VA [auth E] MOL2 format, chain W [auth B] MOL2 format, chain X [auth B] mmCIF format, chain AB [auth F] mmCIF format, chain BB [auth F] mmCIF format, chain CA [auth C] mmCIF format, chain CB [auth F] mmCIF format, chain DA [auth C] mmCIF format, chain DB [auth F] mmCIF format, chain EA [auth C] mmCIF format, chain FA [auth C] mmCIF format, chain KA [auth D] mmCIF format, chain LA [auth D] mmCIF format, chain M [auth A] mmCIF format, chain MA [auth D] mmCIF format, chain N [auth A] mmCIF format, chain NA [auth D] mmCIF format, chain O [auth A] mmCIF format, chain P [auth A] mmCIF format, chain SA [auth E] mmCIF format, chain TA [auth E] mmCIF format, chain U [auth B] mmCIF format, chain UA [auth E] mmCIF format, chain V [auth B] mmCIF format, chain VA [auth E] mmCIF format, chain W [auth B] mmCIF format, chain X [auth B]	AB [auth F] BB [auth F] CA [auth C] CB [auth F] DA [auth C] AB [auth F], BB [auth F], CA [auth C], CB [auth F], DA [auth C], DB [auth F], EA [auth C], FA [auth C], KA [auth D], LA [auth D], M [auth A], MA [auth D], N [auth A], NA [auth D], O [auth A], P [auth A], SA [auth E], TA [auth E], U [auth B], UA [auth E], V [auth B], VA [auth E], W [auth B], X [auth B]	FORMIC ACID C H₂ O₂ BDAGIHXWWSANSR-UHFFFAOYSA-N		Interactions Focus chain AB [auth F] Focus chain BB [auth F] Focus chain CA [auth C] Focus chain CB [auth F] Focus chain DA [auth C] Focus chain DB [auth F] Focus chain EA [auth C] Focus chain FA [auth C] Focus chain KA [auth D] Focus chain LA [auth D] Focus chain M [auth A] Focus chain MA [auth D] Focus chain N [auth A] Focus chain NA [auth D] Focus chain O [auth A] Focus chain P [auth A] Focus chain SA [auth E] Focus chain TA [auth E] Focus chain U [auth B] Focus chain UA [auth E] Focus chain V [auth B] Focus chain VA [auth E] Focus chain W [auth B] Focus chain X [auth B] Interactions & Density Focus chain AB [auth F] Focus chain BB [auth F] Focus chain CA [auth C] Focus chain CB [auth F] Focus chain DA [auth C] Focus chain DB [auth F] Focus chain EA [auth C] Focus chain FA [auth C] Focus chain KA [auth D] Focus chain LA [auth D] Focus chain M [auth A] Focus chain MA [auth D] Focus chain N [auth A] Focus chain NA [auth D] Focus chain O [auth A] Focus chain P [auth A] Focus chain SA [auth E] Focus chain TA [auth E] Focus chain U [auth B] Focus chain UA [auth E] Focus chain V [auth B] Focus chain VA [auth E] Focus chain W [auth B] Focus chain X [auth B]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain AA [auth B] SDF format, chain EB [auth F] SDF format, chain FB [auth F] SDF format, chain GA [auth C] SDF format, chain GB [auth F] SDF format, chain HA [auth C] SDF format, chain IA [auth C] SDF format, chain OA [auth D] SDF format, chain PA [auth D] SDF format, chain Q [auth A] SDF format, chain QA [auth D] SDF format, chain R [auth A] SDF format, chain S [auth A] SDF format, chain WA [auth E] SDF format, chain XA [auth E] SDF format, chain Y [auth B] SDF format, chain YA [auth E] SDF format, chain Z [auth B] MOL2 format, chain AA [auth B] MOL2 format, chain EB [auth F] MOL2 format, chain FB [auth F] MOL2 format, chain GA [auth C] MOL2 format, chain GB [auth F] MOL2 format, chain HA [auth C] MOL2 format, chain IA [auth C] MOL2 format, chain OA [auth D] MOL2 format, chain PA [auth D] MOL2 format, chain Q [auth A] MOL2 format, chain QA [auth D] MOL2 format, chain R [auth A] MOL2 format, chain S [auth A] MOL2 format, chain WA [auth E] MOL2 format, chain XA [auth E] MOL2 format, chain Y [auth B] MOL2 format, chain YA [auth E] MOL2 format, chain Z [auth B] mmCIF format, chain AA [auth B] mmCIF format, chain EB [auth F] mmCIF format, chain FB [auth F] mmCIF format, chain GA [auth C] mmCIF format, chain GB [auth F] mmCIF format, chain HA [auth C] mmCIF format, chain IA [auth C] mmCIF format, chain OA [auth D] mmCIF format, chain PA [auth D] mmCIF format, chain Q [auth A] mmCIF format, chain QA [auth D] mmCIF format, chain R [auth A] mmCIF format, chain S [auth A] mmCIF format, chain WA [auth E] mmCIF format, chain XA [auth E] mmCIF format, chain Y [auth B] mmCIF format, chain YA [auth E] mmCIF format, chain Z [auth B]	AA [auth B] EB [auth F] FB [auth F] GA [auth C] GB [auth F] AA [auth B], EB [auth F], FB [auth F], GA [auth C], GB [auth F], HA [auth C], IA [auth C], OA [auth D], PA [auth D], Q [auth A], QA [auth D], R [auth A], S [auth A], WA [auth E], XA [auth E], Y [auth B], YA [auth E], Z [auth B]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain AA [auth B] Focus chain EB [auth F] Focus chain FB [auth F] Focus chain GA [auth C] Focus chain GB [auth F] Focus chain HA [auth C] Focus chain IA [auth C] Focus chain OA [auth D] Focus chain PA [auth D] Focus chain Q [auth A] Focus chain QA [auth D] Focus chain R [auth A] Focus chain S [auth A] Focus chain WA [auth E] Focus chain XA [auth E] Focus chain Y [auth B] Focus chain YA [auth E] Focus chain Z [auth B] Interactions & Density Focus chain AA [auth B] Focus chain EB [auth F] Focus chain FB [auth F] Focus chain GA [auth C] Focus chain GB [auth F] Focus chain HA [auth C] Focus chain IA [auth C] Focus chain OA [auth D] Focus chain PA [auth D] Focus chain Q [auth A] Focus chain QA [auth D] Focus chain R [auth A] Focus chain S [auth A] Focus chain WA [auth E] Focus chain XA [auth E] Focus chain Y [auth B] Focus chain YA [auth E] Focus chain Z [auth B]
NA Query on NA Download Ideal Coordinates CCD File SDF format, chain BA [auth B] SDF format, chain HB [auth F] SDF format, chain JA [auth C] SDF format, chain RA [auth D] SDF format, chain T [auth A] SDF format, chain ZA [auth E] MOL2 format, chain BA [auth B] MOL2 format, chain HB [auth F] MOL2 format, chain JA [auth C] MOL2 format, chain RA [auth D] MOL2 format, chain T [auth A] MOL2 format, chain ZA [auth E] mmCIF format, chain BA [auth B] mmCIF format, chain HB [auth F] mmCIF format, chain JA [auth C] mmCIF format, chain RA [auth D] mmCIF format, chain T [auth A] mmCIF format, chain ZA [auth E]	BA [auth B] HB [auth F] JA [auth C] RA [auth D] T [auth A] BA [auth B], HB [auth F], JA [auth C], RA [auth D], T [auth A], ZA [auth E]	SODIUM ION Na FKNQFGJONOIPTF-UHFFFAOYSA-N		Interactions Focus chain BA [auth B] Focus chain HB [auth F] Focus chain JA [auth C] Focus chain RA [auth D] Focus chain T [auth A] Focus chain ZA [auth E] Interactions & Density Focus chain BA [auth B] Focus chain HB [auth F] Focus chain JA [auth C] Focus chain RA [auth D] Focus chain T [auth A] Focus chain ZA [auth E]

Biologically Interesting Molecules (External Reference) 1 Unique

Entity ID: 2
ID	Chains	Name	Type/Class	2D Diagram	3D Interactions
PRD_001220 Query on PRD_001220	G [auth H] H [auth I] I [auth J] J [auth K] K [auth L] G [auth H], H [auth I], I [auth J], J [auth K], K [auth L], L [auth N]	meta-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)benzamidine	Polypeptide / Enzyme inhibitor		Interactions Focus chain G [auth H] Focus chain H [auth I] Focus chain I [auth J] Focus chain J [auth K] Focus chain K [auth L] Focus chain L [auth N] Interactions & Density Focus chain G [auth H] Focus chain H [auth I] Focus chain I [auth J] Focus chain J [auth K] Focus chain K [auth L] Focus chain L [auth N]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.30 Å
R-Value Free: 0.216
R-Value Work: 0.185
Space Group: P 2₁ 2₁ 2₁

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 141.178	α = 90
b = 152.849	β = 90
c = 168.306	γ = 90

Software Package:

Software Name	Purpose
MxCuBE	data collection
PHASER	phasing
CNS	refinement
XDS	data reduction
XDS	data scaling

Structure Validation

View Full Validation Report

Entry History

Deposition Data

Released Date: 2014-04-09

Deposition Author(s):

Dahms, S.O.

Than, M.E.

Revision History (Full details and data files)

Version 1.0: 2014-04-09
Type: Initial release
Version 1.1: 2014-05-28
Changes: Database references
Version 2.0: 2024-11-27
Changes: Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Structure summary