1zap

From Proteopedia

(Difference between revisions)

Current revision

SECRETED ASPARTIC PROTEASE FROM C. ALBICANS

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:	,
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).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] 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).^[9] ^[10] ^[11]

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^[12]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Schaller M, Januschke E, Schackert C, Woerle B, Korting HC. Different isoforms of secreted aspartyl proteinases (Sap) are expressed by Candida albicans during oral and cutaneous candidosis in vivo. J Med Microbiol. 2001 Aug;50(8):743-7. PMID:11478679
↑ Schaller M, Bein M, Korting HC, Baur S, Hamm G, Monod M, Beinhauer S, Hube B. The secreted aspartyl proteinases Sap1 and Sap2 cause tissue damage in an in vitro model of vaginal candidiasis based on reconstituted human vaginal epithelium. Infect Immun. 2003 Jun;71(6):3227-34. PMID:12761103 doi:10.1128/IAI.71.6.3227-3234.2003
↑ Copping VM, Barelle CJ, Hube B, Gow NA, Brown AJ, Odds FC. Exposure of Candida albicans to antifungal agents affects expression of SAP2 and SAP9 secreted proteinase genes. J Antimicrob Chemother. 2005 May;55(5):645-54. PMID:15820985 doi:10.1093/jac/dki088
↑ Schaller M, Korting HC, Borelli C, Hamm G, Hube B. Candida albicans-secreted aspartic proteinases modify the epithelial cytokine response in an in vitro model of vaginal candidiasis. Infect Immun. 2005 May;73(5):2758-65. PMID:15845479 doi:10.1128/IAI.73.5.2758-2765.2005
↑ Gropp K, Schild L, Schindler S, Hube B, Zipfel PF, Skerka C. The yeast Candida albicans evades human complement attack by secretion of aspartic proteases. Mol Immunol. 2009 Dec;47(2-3):465-75. PMID:19880183 doi:10.1016/j.molimm.2009.08.019
↑ Pietrella D, Rachini A, Pandey N, Schild L, Netea M, Bistoni F, Hube B, Vecchiarelli A. The Inflammatory response induced by aspartic proteases of Candida albicans is independent of proteolytic activity. Infect Immun. 2010 Nov;78(11):4754-62. PMID:20713630 doi:10.1128/IAI.00789-10
↑ Ramage G, Coco B, Sherry L, Bagg J, Lappin DF. In vitro Candida albicans biofilm induced proteinase activity and SAP8 expression correlates with in vivo denture stomatitis severity. Mycopathologia. 2012 Jul;174(1):11-19. PMID:22302440 doi:10.1007/s11046-012-9522-2
↑ Bochenska O, Rapala-Kozik M, Wolak N, Bras G, Kozik A, Dubin A, Aoki W, Ueda M, Mak P. Secreted aspartic peptidases of Candida albicans liberate bactericidal hemocidins from human hemoglobin. Peptides. 2013 Oct;48:49-58. doi: 10.1016/j.peptides.2013.07.023. Epub 2013 Aug, 6. PMID:23927842 doi:http://dx.doi.org/10.1016/j.peptides.2013.07.023
↑ Bochenska O, Rapala-Kozik M, Wolak N, Aoki W, Ueda M, Kozik A. The action of ten secreted aspartic proteases of pathogenic yeast Candida albicans on major human salivary antimicrobial peptide, histatin 5. Acta Biochim Pol. 2016;63(3):403-10. PMID:27390786 doi:10.18388/abp.2016_1318
↑ Ikonomova SP, Moghaddam-Taaheri P, Jabra-Rizk MA, Wang Y, Karlsson AJ. Engineering improved variants of the antifungal peptide histatin 5 with reduced susceptibility to Candida albicans secreted aspartic proteases and enhanced antimicrobial potency. FEBS J. 2018 Jan;285(1):146-159. PMID:29143452 doi:10.1111/febs.14327
↑ Ikonomova SP, Moghaddam-Taaheri P, Wang Y, Doolin MT, Stroka KM, Hube B, Karlsson AJ. Effects of histatin 5 modifications on antifungal activity and kinetics of proteolysis. Protein Sci. 2020 Feb;29(2):480-493. PMID:31675138 doi:10.1002/pro.3767
↑ Abad-Zapatero C, Goldman R, Muchmore SW, Hutchins C, Stewart K, Navaza J, Payne CD, Ray TL. Structure of a secreted aspartic protease from C. albicans complexed with a potent inhibitor: implications for the design of antifungal agents. Protein Sci. 1996 Apr;5(4):640-52. PMID:8845753

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1zap"

Categories: Candida albicans | Large Structures | Abad-Zapatero C | Muchmore SW

@@ Line 1: / Line 1: @@
-[[Image:1zap.gif|left|200px]]<br /><applet load="1zap" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="1zap, resolution 2.5&Aring;" />
-'''SECRETED ASPARTIC PROTEASE FROM C. ALBICANS'''<br />
-==Overview==
+==SECRETED ASPARTIC PROTEASE FROM C. ALBICANS==
-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.
+<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].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== 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.
-==About this Structure==
+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>
-ZAP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Candida_albicans Candida albicans] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=A70:'>A70</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Candidapepsin Candidapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.24 3.4.23.24] Known structural/functional Site: <scene name='pdbsite=ACT:Aspartic+Proteinases+Are+Characterized+By+Two+ASP+Residu+...'>ACT</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZAP OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8845753 8845753]
+</div>
-[[Category: Candida albicans]]
+<div class="pdbe-citations 1zap" style="background-color:#fffaf0;"></div>
-[[Category: Candidapepsin]]
-[[Category: Single protein]]
-[[Category: Abad-Zapatero, C.]]
-[[Category: Muchmore, S.W.]]
-[[Category: A70]]
-[[Category: ZN]]
-[[Category: aspartic protease]]
-[[Category: candida albicans]]
-[[Category: secreted]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb  3 10:22:37 2008''
+==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]]

1zap

From Proteopedia

Current revision

SECRETED ASPARTIC PROTEASE FROM C. ALBICANS

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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