ISDA: 5WKM

Deposition Date 2017-07-25

Release Date 2018-04-04

Last Version Date 2024-11-06

Entry Detail

PDB ID:

5WKM

Keywords:

HYDROLASE/HYDROLASE INHIBITOR

Title:

2.25 A resolution structure of MERS 3CL protease in complex with piperidine-based peptidomimetic inhibitor 21

Biological Source:

Source Organism(s):

Middle East respiratory syndrome-related coronavirus (Taxon ID: 1335626)

Expression System(s):

Escherichia coli

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

2.25 Å

R-Value Free:

0.22

R-Value Work:

0.16

R-Value Observed:

0.16

Space Group:

C 1 2 1

Download Validation Report

Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Orf1a protein
Chain IDs:A
Chain Length:313
Number of Molecules:1
Biological Source:Middle East respiratory syndrome-related coronavirus

UniProt ID:K9N638 Pfam ID:PF05409

Ligand Molecules

B6Y

N02

Primary Citation

Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element.

Galasiti Kankanamalage, A.C, Kim, Y, Damalanka, V.C, Rathnayake, A.D, Fehr, A.R, Mehzabeen, N, Battaile, K.P, Lovell, S, Lushington, G.H, Perlman, S, Chang, K.O, Groutas, W.C.Show

Eur J Med Chem 150 334 346 (2018)

PMID: 29544147 DOI: 10.1016/j.ejmech.2018.03.004

Abstact

There are currently no approved vaccines or small molecule therapeutics available for the prophylaxis or treatment of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections. MERS-CoV 3CL protease is essential for viral replication; consequently, it is an attractive target that provides a potentially effective means of developing small molecule therapeutics for combatting MERS-CoV. We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The mechanism of action of the compounds and the structural determinants associated with binding were illuminated using X-ray crystallography.

Legend

Protein

Chemical

Disease

Primary Citation of related structures

Abstact

Feedback Form