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| | ==Serine Protease HtrA3, mutationally inactivated== | | ==Serine Protease HtrA3, mutationally inactivated== |
| - | <StructureSection load='4ri0' size='340' side='right' caption='[[4ri0]], [[Resolution|resolution]] 3.27Å' scene=''> | + | <StructureSection load='4ri0' size='340' side='right'caption='[[4ri0]], [[Resolution|resolution]] 3.27Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ri0]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RI0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RI0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ri0]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RI0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RI0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 3.272Å</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=4ri0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ri0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ri0 RCSB], [http://www.ebi.ac.uk/pdbsum/4ri0 PDBsum]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4ri0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ri0 OCA], [https://pdbe.org/4ri0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ri0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ri0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ri0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HTRA3_HUMAN HTRA3_HUMAN]] Serine protease that cleaves beta-casein/CSN2 as well as several extracellular matrix (ECM) proteoglycans such as decorin/DCN, biglycan/BGN and fibronectin/FN1. Inhibits signaling mediated by TGF-beta family proteins possibly indirectly by degradation of these ECM proteoglycans (By similarity). May act as a tumor suppressor. Negatively regulates, in vitro, trophoblast invasion during placental development and may be involved in the development of the placenta in vivo. May also have a role in ovarian development, granulosa cell differentiation and luteinization.<ref>PMID:21321049</ref> | + | [https://www.uniprot.org/uniprot/HTRA3_HUMAN HTRA3_HUMAN] Serine protease that cleaves beta-casein/CSN2 as well as several extracellular matrix (ECM) proteoglycans such as decorin/DCN, biglycan/BGN and fibronectin/FN1. Inhibits signaling mediated by TGF-beta family proteins possibly indirectly by degradation of these ECM proteoglycans (By similarity). May act as a tumor suppressor. Negatively regulates, in vitro, trophoblast invasion during placental development and may be involved in the development of the placenta in vivo. May also have a role in ovarian development, granulosa cell differentiation and luteinization.<ref>PMID:21321049</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4ri0" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glaza, P]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Joachimiak, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Lipinska, B]] | + | [[Category: Glaza P]] |
| - | [[Category: Structural genomic]] | + | [[Category: Joachimiak A]] |
| - | [[Category: Osipiuk, J]] | + | [[Category: Lipinska B]] |
| - | [[Category: Wenta, T]] | + | [[Category: Osipiuk J]] |
| - | [[Category: Hydrolase]] | + | [[Category: Wenta T]] |
| - | [[Category: Mcsg]]
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| - | [[Category: National science center - poland]]
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| - | [[Category: Protease]]
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| - | [[Category: Psi-biology]]
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| Structural highlights
Function
HTRA3_HUMAN Serine protease that cleaves beta-casein/CSN2 as well as several extracellular matrix (ECM) proteoglycans such as decorin/DCN, biglycan/BGN and fibronectin/FN1. Inhibits signaling mediated by TGF-beta family proteins possibly indirectly by degradation of these ECM proteoglycans (By similarity). May act as a tumor suppressor. Negatively regulates, in vitro, trophoblast invasion during placental development and may be involved in the development of the placenta in vivo. May also have a role in ovarian development, granulosa cell differentiation and luteinization.[1]
Publication Abstract from PubMed
Human HtrA3 protease, which induces mitochondria-mediated apoptosis, can be a tumor suppressor and a potential therapeutic target in the treatment of cancer. However, there is little information about its structure and biochemical properties. HtrA3 is composed of an N-terminal domain not required for proteolytic activity, a central serine protease domain and a C-terminal PDZ domain. HtrA3S, its short natural isoform, lacks the PDZ domain which is substituted by a stretch of 7 C-terminal amino acid residues, unique for this isoform. This paper presents the crystal structure of the HtrA3 protease domain together with the PDZ domain (DeltaN-HtrA3), showing that the protein forms a trimer whose protease domains are similar to those of human HtrA1 and HtrA2. The DeltaN-HtrA3 PDZ domains are placed in a position intermediate between that in the flat saucer-like HtrA1 SAXS structure and the compact pyramidal HtrA2 X-ray structure. The PDZ domain interacts closely with the LB loop of the protease domain in a way not found in other human HtrAs. DeltaN-HtrA3 with the PDZ removed (DeltaN-HtrA3-DeltaPDZ) and an N-terminally truncated HtrA3S (DeltaN-HtrA3S) were fully active at a wide range of temperatures and their substrate affinity was not impaired. This indicates that the PDZ domain is dispensable for HtrA3 activity. As determined by size exclusion chromatography, DeltaN-HtrA3 formed stable trimers while both DeltaN-HtrA3-DeltaPDZ and DeltaN-HtrA3S were monomeric. This suggests that the presence of the PDZ domain, unlike in HtrA1 and HtrA2, influences HtrA3 trimer formation. The unique C-terminal sequence of DeltaN-HtrA3S appeared to have little effect on activity and oligomerization. Additionally, we examined the cleavage specificity of DeltaN-HtrA3. Results reported in this paper provide new insights into the structure and function of DeltaN-HtrA3, which seems to have a unique combination of features among human HtrA proteases.
Structural and Functional Analysis of Human HtrA3 Protease and Its Subdomains.,Glaza P, Osipiuk J, Wenta T, Zurawa-Janicka D, Jarzab M, Lesner A, Banecki B, Skorko-Glonek J, Joachimiak A, Lipinska B PLoS One. 2015 Jun 25;10(6):e0131142. doi: 10.1371/journal.pone.0131142., eCollection 2015. PMID:26110759[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Singh H, Endo Y, Nie G. Decidual HtrA3 negatively regulates trophoblast invasion during human placentation. Hum Reprod. 2011 Apr;26(4):748-57. doi: 10.1093/humrep/der019. Epub 2011 Feb 14. PMID:21321049 doi:http://dx.doi.org/10.1093/humrep/der019
- ↑ Glaza P, Osipiuk J, Wenta T, Zurawa-Janicka D, Jarzab M, Lesner A, Banecki B, Skorko-Glonek J, Joachimiak A, Lipinska B. Structural and Functional Analysis of Human HtrA3 Protease and Its Subdomains. PLoS One. 2015 Jun 25;10(6):e0131142. doi: 10.1371/journal.pone.0131142., eCollection 2015. PMID:26110759 doi:http://dx.doi.org/10.1371/journal.pone.0131142
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