1PWQ

Crystal structure of Anthrax Lethal Factor complexed with Thioacetyl-Tyr-Pro-Met-Amide, a metal-chelating peptidyl small molecule inhibitor

Summary for 1PWQ

• Entry DOI: 10.2210/pdb1pwq/pdb
• Related: 1PWP
• Descriptor: Lethal factor, ZINC ION, N-(SULFANYLACETYL)TYROSYLPROLYLMETHIONINAMIDE (3 entities in total)
• Functional Keywords: anthrax toxin, lethal factor, metal-chelator, small molecule peptidic inhibitor, hydrolase
• Biological source: Bacillus anthracis
• Cellular location: Secreted: P15917
• Total number of polymer chains: 2
• Total formula weight: 181809.68

Authors

Wong, T.Y.,Schwarzenbacher, R.,Liddington, R.C. (deposition date: 2003-07-02, release date: 2004-01-13, Last modification date: 2023-08-16)

Primary citation

Turk, B.E.,Wong, T.Y.,Schwarzenbacher, R.,Jarrell, E.T.,Leppla, S.H.,Collier, R.J.,Liddington, R.C.,Cantley, L.C.
The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor.
Nat.Struct.Mol.Biol., 11:60-66, 2004

PubMed Abstract: Recent events have created an urgent need for new therapeutic strategies to treat anthrax. We have applied a mixture-based peptide library approach to rapidly determine the optimal peptide substrate for the anthrax lethal factor (LF), a metalloproteinase with an important role in the pathogenesis of the disease. Using this approach we have identified peptide analogs that inhibit the enzyme in vitro and that protect cultured macrophages from LF-mediated cytolysis. The crystal structures of LF bound to an optimized peptide substrate and to peptide-based inhibitors provide a rationale for the observed selectivity and may be exploited in the design of future generations of LF inhibitors.

PubMed: 14718924
DOI: 10.1038/nsmb708

Experimental method

X-RAY DIFFRACTION (3.52 Å)