View source for 1zap


==SECRETED ASPARTIC PROTEASE FROM C. ALBICANS==
<StructureSection load='1zap' size='340' side='right'caption='[[1zap]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1zap]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans Candida albicans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZAP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A70:N-ETHYL-N-[(4-METHYLPIPERAZIN-1-YL)CARBONYL]-D-PHENYLALANYL-N-[(1S,2S,4R)-4-(BUTYLCARBAMOYL)-1-(CYCLOHEXYLMETHYL)-2-HYDROXY-5-METHYLHEXYL]-L-NORLEUCINAMIDE'>A70</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zap OCA], [https://pdbe.org/1zap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zap RCSB], [https://www.ebi.ac.uk/pdbsum/1zap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zap ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CARP2_CANAX 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).<ref>PMID:11478679</ref> <ref>PMID:12761103</ref> <ref>PMID:15820985</ref> <ref>PMID:15845479</ref> <ref>PMID:19880183</ref> <ref>PMID:20713630</ref> <ref>PMID:22302440</ref> <ref>PMID:23927842</ref>   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).<ref>PMID:27390786</ref> <ref>PMID:29143452</ref> <ref>PMID:31675138</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/za/1zap_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1zap ConSurf].
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== 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<ref>PMID:8845753</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1zap" style="background-color:#fffaf0;"></div>

==See Also==
*[[Proteinase 3D structures|Proteinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Candida albicans]]
[[Category: Large Structures]]
[[Category: Abad-Zapatero C]]
[[Category: Muchmore SW]]