7AGC

Protease Sapp1p from Candida parapsilosis in complex with KB74

Summary for 7AGC

• Entry DOI: 10.2210/pdb7agc/pdb
• Related: 3FV3
• Descriptor: Candidapepsin, KB74, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (7 entities in total)
• Functional Keywords: secreted aspartic protease, virulence factor, candidiasis, peptidomimetic inhibitors, antibiotic
• Biological source: Candida parapsilosis; More
• Total number of polymer chains: 8
• Total formula weight: 147502.40

Authors

Dostal, J.,Heidingsfeld, O.,Brynda, J. (deposition date: 2020-09-22, release date: 2021-04-21, Last modification date: 2024-05-29)

Primary citation

Dostal, J.,Brynda, J.,Vankova, L.,Zia, S.R.,Pichova, I.,Heidingsfeld, O.,Lepsik, M.
Structural determinants for subnanomolar inhibition of the secreted aspartic protease Sapp1p from Candida parapsilosis .
J Enzyme Inhib Med Chem, 36:914-921, 2021

PubMed Abstract: Pathogenic yeasts frequently cause infections in hospitals. Antifungal drugs lose effectiveness due to other species and resistance. New medications are thus required. Secreted aspartic protease of (Sapp1p) is a promising target. We have thus solved the crystal structures of Sapp1p complexed to four peptidomimetic inhibitors. Three potent inhibitors (K: 0.1, 0.4, 6.6 nM) resembled pepstatin A (K: 0.3 nM), a general aspartic protease inhibitor, in terms of their interactions with Sapp1p. However, the weaker inhibitor (K: 14.6 nM) formed fewer nonpolar contacts with Sapp1p, similarly to the smaller HIV protease inhibitor ritonavir (K: 1.9 µM), which, moreover, formed fewer H-bonds. The analyses have revealed the structural determinants of the subnanomolar inhibition of aspartic protease. Because of the high similarity between Saps from different species, these results can further be used for the design of potent and specific Sap inhibitor-based antimycotic drugs.

PubMed: 33843395
DOI: 10.1080/14756366.2021.1906664

Experimental method

X-RAY DIFFRACTION (1.35 Å)