4WF6: Anthrax Toxin Lethal Factor With Bound Small Molecule Inhibitor Mk-31

Citation:
Abstract
The lethal factor (LF) enzyme secreted by Bacillus anthracis is a zinc hydrolase that is chiefly responsible for anthrax-related cell death. Although many studies of the design of small molecule LF inhibitors have been conducted, no LF inhibitor is yet available as a therapeutic agent. Inhibitors with considerable chemical diversity have been developed and investigated; however, the LF S2' subsite has not yet been systematically explored as a potential target for lead optimization. Here we present synthesis, experimental evaluation, modeling, and structural biology for a novel series of sulfonamide hydroxamate LF inhibitor analogues specifically designed to extend into, and probe chemical preferences of, this S2' subsite. We discovered that this region accommodates a wide variety of chemical functionalities and that a broad selection of ligand structural modifications directed to this area can be incorporated without significant deleterious alterations in biological activity. We also identified key residues in this subsite that can potentially be targeted to improve inhibitor binding.
PDB ID: 4WF6Download
MMDB ID: 132391
PDB Deposition Date: 2014/9/12
Updated in MMDB: 2015/11
Experimental Method:
x-ray diffraction
Resolution: 2.65  Å
Source Organism:
Similar Structures:
Biological Unit for 4WF6: monomeric; determined by author
Molecular Components in 4WF6
Label Count Molecule
Protein (1 molecule)
1
Lethal Factor(Gene symbol: pxo1_107)
Molecule annotation
Chemicals (3 molecules)
1
1
2
1
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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