5HYO

X-Ray Structure of Unbound Porcine Epidemic Diarrhea Virus 3CLpro


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.208 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

X-Ray Structure and Inhibition of 3C-like Protease from Porcine Epidemic Diarrhea Virus.

St John, S.E.Anson, B.J.Mesecar, A.D.

(2016) Sci Rep 6: 25961-25961

  • DOI: https://doi.org/10.1038/srep25961
  • Primary Citation of Related Structures:  
    5HYO

  • PubMed Abstract: 

    Porcine epidemic diarrhea virus (PEDV) is a coronavirus that infects pigs and can have mortality rates approaching 100% in piglets, causing serious economic impact. The 3C-like protease (3CL(pro)) is essential for the coronaviral life cycle and is an appealing target for the development of therapeutics. We report the expression, purification, crystallization and 2.10 Å X-ray structure of 3CL(pro) from PEDV. Analysis of the PEDV 3CL(pro) structure and comparison to other coronaviral 3CL(pro)'s from the same alpha-coronavirus phylogeny shows that the overall structures and active site architectures across 3CL(pro)'s are conserved, with the exception of a loop that comprises the protease S2 pocket. We found a known inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL(pro), (R)-16, to have inhibitor activity against PEDV 3CL(pro), despite that SARS-3CL(pro) and PEDV 3CL(pro) share only 45.4% sequence identity. Structural comparison reveals that the majority of residues involved in (R)-16 binding to SARS-3CL(pro) are conserved in PEDV-3CL(pro); however, the sequence variation and positional difference in the loop forming the S2 pocket may account for large observed difference in IC50 values. This work advances our understanding of the subtle, but important, differences in coronaviral 3CL(pro) architecture and contributes to the broader structural knowledge of coronaviral 3CL(pro)'s.


  • Organizational Affiliation

    Department of Chemistry, Purdue University, West Lafayette, Indiana, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PEDV 3CLpro
A, B
301Porcine epidemic diarrhea virusMutation(s): 0 
UniProt
Find proteins for U6BPB2 (Porcine epidemic diarrhea virus)
Explore U6BPB2 
Go to UniProtKB:  U6BPB2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupU6BPB2
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MPD
Query on MPD

Download Ideal Coordinates CCD File 
H [auth A],
L [auth B]
(4S)-2-METHYL-2,4-PENTANEDIOL
C6 H14 O2
SVTBMSDMJJWYQN-YFKPBYRVSA-N
DMS
Query on DMS

Download Ideal Coordinates CCD File 
I [auth A]DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
IPA
Query on IPA

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
J [auth B],
K [auth B]
ISOPROPYL ALCOHOL
C3 H8 O
KFZMGEQAYNKOFK-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.208 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 58.586α = 90
b = 76.292β = 90
c = 119.169γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI085089
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesAI26603

Revision History  (Full details and data files)

  • Version 1.0: 2016-06-01
    Type: Initial release
  • Version 1.1: 2017-09-20
    Changes: Author supporting evidence, Derived calculations
  • Version 1.2: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.3: 2024-03-06
    Changes: Data collection, Database references