6C2M

Crystal structure of HCV NS3/4A protease variant Y56H in complex with MK-5172

PDB DOI: https://doi.org/10.2210/pdb6C2M/pdb

Classification: HYDROLASE/HYDROLASE Inhibitor
Organism(s): Hepacivirus hominis
Expression System: Escherichia coli BL21(DE3)
Mutation(s): Yes

Deposited: 2018-01-08 Released: 2019-01-16
Deposition Author(s): Matthew, A.N., Schiffer, C.A.
Funding Organization(s): National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID), National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.86 Å
R-Value Free: 0.224
R-Value Work: 0.180
R-Value Observed: 0.184

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.4 of the entry. See complete history.

Literature

Clinical signature variant of HCV NS3/4A protease uses a novel mechanism to confer resistance

Matthew, A.N., Schiffer, C.A.

To be published.

Macromolecule Content

Total Structure Weight: 86.84 kDa
Atom Count: 5,828
Modelled Residue Count: 764
Deposited Residue Count: 788
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
NS3 protease	A, B, C, D	197	Hepacivirus hominis	Mutation(s): 12
UniProt
Find proteins for C1KIK8 (Hepacivirus hominis) Explore C1KIK8 Go to UniProtKB: C1KIK8
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	C1KIK8
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
SUE Query on SUE Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain H [auth B] SDF format, chain M [auth D] SDF format, chain K [auth C] MOL2 format, chain F [auth A] MOL2 format, chain H [auth B] MOL2 format, chain M [auth D] MOL2 format, chain K [auth C] mmCIF format, chain F [auth A] mmCIF format, chain H [auth B] mmCIF format, chain M [auth D] mmCIF format, chain K [auth C]	F [auth A], H [auth B], K [auth C], M [auth D]	(1aR,5S,8S,10R,22aR)-5-tert-butyl-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-14-methoxy-3,6-di oxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadec ino[11,12-b]quinoxaline-8-carboxamide C₃₈ H₅₀ N₆ O₉ S OBMNJSNZOWALQB-NCQNOWPTSA-N		Interactions Focus chain F [auth A] Focus chain H [auth B] Focus chain K [auth C] Focus chain M [auth D] Interactions & Density Focus chain F [auth A] Focus chain H [auth B] Focus chain K [auth C] Focus chain M [auth D]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain I [auth C] MOL2 format, chain I [auth C] mmCIF format, chain I [auth C]	I [auth C]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain I [auth C] Interactions & Density Focus chain I [auth C]
ZN Query on ZN Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain G [auth B] SDF format, chain J [auth C] SDF format, chain L [auth D] MOL2 format, chain E [auth A] MOL2 format, chain G [auth B] MOL2 format, chain J [auth C] MOL2 format, chain L [auth D] mmCIF format, chain E [auth A] mmCIF format, chain G [auth B] mmCIF format, chain J [auth C] mmCIF format, chain L [auth D]	E [auth A], G [auth B], J [auth C], L [auth D]	ZINC ION Zn PTFCDOFLOPIGGS-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain G [auth B] Focus chain J [auth C] Focus chain L [auth D] Interactions & Density Focus chain E [auth A] Focus chain G [auth B] Focus chain J [auth C] Focus chain L [auth D]

Binding Affinity Annotations
ID	Source	Binding Affinity
SUE	BindingDB: 6C2M	Ki: min: 0.14, max: 30 (nM) from 5 assay(s)
SUE	BindingDB: 6C2M	IC50: 2 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.86 Å
R-Value Free: 0.224
R-Value Work: 0.180
R-Value Observed: 0.184
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 56.635	α = 90
b = 103.326	β = 112.01
c = 73.962	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
HKL-3000	data scaling
PHASER	phasing
Coot	model building
HKL-3000	data collection
HKL-3000	data processing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2019-01-16

Deposition Author(s):

Matthew, A.N.

Schiffer, C.A.

Funding Organization	Location	Grant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)	United States	R01 AI085051
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	United States	F31 GM119345

Revision History (Full details and data files)

Version 1.0: 2019-01-16
Type: Initial release
Version 1.1: 2019-02-20
Changes: Author supporting evidence, Data collection
Version 1.2: 2019-12-11
Changes: Structure summary
Version 1.3: 2019-12-18
Changes: Author supporting evidence
Version 1.4: 2023-10-04
Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary