1zap

SECRETED ASPARTIC PROTEASE FROM C. ALBICANS

spinqualitylabelsall models 1zap, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1zap is a 1 chain structure with sequence from Candida albicans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: A70, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CARP2_CANAX Secreted aspartic peptidases (SAPs) are a group of ten acidic hydrolases considered as key virulence factors (PubMed:11478679, PubMed:12761103, PubMed:15820985, PubMed:15845479, PubMed:19880183, PubMed:20713630, PubMed:22302440, PubMed:23927842). These enzymes supply the fungus with nutrient amino acids as well as are able to degrade the selected host's proteins involved in the immune defense (PubMed:11478679, PubMed:12761103, PubMed:15820985, PubMed:15845479, PubMed:19880183, PubMed:20713630, PubMed:22302440, PubMed:23927842). Induces host inflammatory cytokine production in a proteolytic activity-independent way (PubMed:20713630). Plays a role in tissue damage during superficial infection (PubMed:12761103). Moreover, acts toward human hemoglobin though limited proteolysis to generate a variety of antimicrobial hemocidins, enabling to compete with the other microorganisms of the same physiological niche using the microbicidal peptides generated from the host protein (PubMed:23927842). Plays a key role in defense against host by cleaving histatin-5 (Hst 5), a peptide from human saliva that carries out fungicidal activity (PubMed:27390786, PubMed:29143452, PubMed:31675138). The cleavage rate decreases in an order of SAP2 > SAP9 > SAP3 > SAP7 > SAP4 > SAP1 > SAP8 (PubMed:27390786). The first cleavage occurs between residues 'Lys-17' and 'His-18' of Hst 5, giving DSHAKRHHGYKRKFHEK and HHSHRGY peptides (PubMed:27390786). Simultaneously, the DSHAKRHHGYKRK peptide is also formed (PubMed:27390786). Further fragmentation by SAP2 results in FHEK and DSHAKRHHGY products (PubMed:27390786). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The three-dimensional structure of a secreted aspartic protease from Candida albicans complexed with a potent inhibitor reveals variations on the classical aspartic protease theme that dramatically alter the specificity of this class of enzymes. The structure presents: (1) an 8-residue insertion near the first disulfide (Cys 45-Cys 50, pepsin numbering) that results in a broad flap extending toward the active site; (2) a 7-residue deletion replacing helix hN2 (Ser 110-Tyr 114), which enlarges the S3 pocket; (3) a short polar connection between the two rigid body domains that alters their relative orientation and provides certain specificity; and (4) an ordered 11-residue addition at the carboxy terminus. The inhibitor binds in an extended conformation and presents a branched structure at the P3 position. The implications of these findings for the design of potent antifungal agents are discussed. Structure of a secreted aspartic protease from C. albicans complexed with a potent inhibitor: implications for the design of antifungal agents.,Abad-Zapatero C, Goldman R, Muchmore SW, Hutchins C, Stewart K, Navaza J, Payne CD, Ray TL Protein Sci. 1996 Apr;5(4):640-52. PMID:8845753 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Proteinase 3D structures

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