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| | <StructureSection load='4tpv' size='340' side='right'caption='[[4tpv]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='4tpv' size='340' side='right'caption='[[4tpv]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4tpv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ancca Ancca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TPV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TPV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4tpv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ancylostoma_caninum Ancylostoma caninum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TPV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TPV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HPI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=29170 ANCCA])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4tpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tpv OCA], [http://pdbe.org/4tpv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tpv RCSB], [http://www.ebi.ac.uk/pdbsum/4tpv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tpv ProSAT]</span></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=4tpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tpv OCA], [https://pdbe.org/4tpv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tpv RCSB], [https://www.ebi.ac.uk/pdbsum/4tpv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tpv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/HPI_ANCCA HPI_ANCCA] Hookworms inhibitor of platelet aggregation and adhesion (PubMed:10191228). Native protein inhibits platelet aggregation induced by ADP, epinephrine, and thrombin (PubMed:10191228). In addition, it prevents adhesion of resting platelets to immobilized fibrinogen and collagen (PubMed:10191228). May act by binding to glycoprotein IIb/IIIa (ITGA2B/ITGB3) and integrin alpha-2/beta-1 (ITGA1/ITGB1), respectively (PubMed:10191228). It is noteworthy that the recombinant protein fails to inhibit binding to fibrinogen (through ITGA2B/ITGB3) and collagen (through ITGA1/ITGB1) (PubMed:10191228, PubMed:26057788).<ref>PMID:10191228</ref> <ref>PMID:26057788</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ancca]] | + | [[Category: Ancylostoma caninum]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Andersen, J F]] | + | [[Category: Andersen JF]] |
| - | [[Category: Francischetti, I]] | + | [[Category: Francischetti I]] |
| - | [[Category: Ma, D]] | + | [[Category: Ma D]] |
| - | [[Category: Blood clotting]]
| + | |
| - | [[Category: Cysteine-rich/antigen 5/pathogenesis-related 1 cap platelet integrin]]
| + | |
| Structural highlights
Function
HPI_ANCCA Hookworms inhibitor of platelet aggregation and adhesion (PubMed:10191228). Native protein inhibits platelet aggregation induced by ADP, epinephrine, and thrombin (PubMed:10191228). In addition, it prevents adhesion of resting platelets to immobilized fibrinogen and collagen (PubMed:10191228). May act by binding to glycoprotein IIb/IIIa (ITGA2B/ITGB3) and integrin alpha-2/beta-1 (ITGA1/ITGB1), respectively (PubMed:10191228). It is noteworthy that the recombinant protein fails to inhibit binding to fibrinogen (through ITGA2B/ITGB3) and collagen (through ITGA1/ITGB1) (PubMed:10191228, PubMed:26057788).[1] [2]
Publication Abstract from PubMed
Secreted protein components of hookworm species include a number of representatives of the cysteine-rich/antigen 5/pathogenesis-related 1 (CAP) protein family known as Ancylostoma-secreted proteins (ASPs). Some of these have been considered as candidate antigens for the development of vaccines against hookworms. The functions of most CAP superfamily members are poorly understood, but one form, the hookworm platelet inhibitor (HPI), has been isolated as a putative antagonist of the platelet integrins alphaIIbbeta3 and alpha2beta1. Here, the crystal structure of HPI is described and its structural features are examined in relation to its possible function. The HPI structure is similar to those of other ASPs and shows incomplete conservation of the sequence motifs CAP1 and CAP2 that are considered to be diagnostic of CAP superfamily members. The asymmetric unit of the HPI crystal contains a dimer with an extensive interaction interface, but chromatographic measurements indicate that it is primarily monomeric in solution. In the dimeric structure, the putative active-site cleft areas from both monomers are united into a single negatively charged depression. A potential Lys-Gly-Asp disintegrin-like motif was identified in the sequence of HPI, but is not positioned at the apex of a tight turn, making it unlikely that it interacts with the integrin. Recombinant HPI produced in Escherichia coli was found not to inhibit the adhesion of human platelets to collagen or fibrinogen, despite having a native structure as shown by X-ray diffraction. This result corroborates previous analyses of recombinant HPI and suggests that it might require post-translational modification or have a different biological function.
The structure of hookworm platelet inhibitor (HPI), a CAP superfamily member from Ancylostoma caninum.,Ma D, Francischetti IM, Ribeiro JM, Andersen JF Acta Crystallogr F Struct Biol Commun. 2015 Jun 1;71(Pt 6):643-9. doi:, 10.1107/S2053230X1500271X. Epub 2015 May 20. PMID:26057788[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chadderdon RC, Cappello M. The hookworm platelet inhibitor: functional blockade of integrins GPIIb/IIIa (alphaIIbbeta3) and GPIa/IIa (alpha2beta1) inhibits platelet aggregation and adhesion in vitro. J Infect Dis. 1999 May;179(5):1235-41. PMID:10191228 doi:10.1086/314724
- ↑ Ma D, Francischetti IM, Ribeiro JM, Andersen JF. The structure of hookworm platelet inhibitor (HPI), a CAP superfamily member from Ancylostoma caninum. Acta Crystallogr F Struct Biol Commun. 2015 Jun 1;71(Pt 6):643-9. doi:, 10.1107/S2053230X1500271X. Epub 2015 May 20. PMID:26057788 doi:http://dx.doi.org/10.1107/S2053230X1500271X
- ↑ Ma D, Francischetti IM, Ribeiro JM, Andersen JF. The structure of hookworm platelet inhibitor (HPI), a CAP superfamily member from Ancylostoma caninum. Acta Crystallogr F Struct Biol Commun. 2015 Jun 1;71(Pt 6):643-9. doi:, 10.1107/S2053230X1500271X. Epub 2015 May 20. PMID:26057788 doi:http://dx.doi.org/10.1107/S2053230X1500271X
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