8a7d: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 8a7d is ~~ON HOLD until Paper~~ Publication

==Partial dimer complex of PAPP-A and its inhibitor STC2==

== Structural highlights ==

<table><tr><td colspan='2'>[[8a7d]] 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=8A7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A7D FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=8a7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a7d OCA], [https://pdbe.org/8a7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a7d RCSB], [https://www.ebi.ac.uk/pdbsum/8a7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a7d ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/PAPP1_HUMAN PAPP1_HUMAN] Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is slightly inhibited by the presence of IGF.<ref>PMID:10077652</ref> <ref>PMID:10913121</ref> <ref>PMID:11522292</ref>

== Publication Abstract from PubMed ==

The metzincin metalloproteinase PAPP-A plays a key role in the regulation of insulin-like growth factor (IGF) signaling by specific cleavage of inhibitory IGF binding proteins (IGFBPs). Using single-particle cryo-electron microscopy (cryo-EM), we here report the structure of PAPP-A in complex with its endogenous inhibitor, stanniocalcin-2 (STC2), neither of which have been reported before. The highest resolution (3.1 A) was obtained for the STC2 subunit and the N-terminal approximately 1000 residues of the PAPP-A subunit. The 500 kDa 2:2 PAPP-A.STC2 complex is a flexible multidomain ensemble with numerous interdomain contacts. In particular, a specific disulfide bond between the subunits of STC2 and PAPP-A prevents dissociation, and interactions between STC2 and a module located in the very C-terminal end of the PAPP-A subunit prevent binding of its main substrate, IGFBP-4. While devoid of activity towards IGFBP-4, the active site cleft of the catalytic domain is accessible in the inhibited PAPP-A.STC2 complex, as shown by its ability to hydrolyze a synthetic peptide derived from IGFBP-4. Relevant to multiple human pathologies, this unusual mechanism of proteolytic inhibition may support the development of specific pharmaceutical agents, by which IGF signaling can be indirectly modulated.

~~Authors~~:

Structure of the proteolytic enzyme PAPP-A with the endogenous inhibitor stanniocalcin-2 reveals its inhibitory mechanism.,Kobbero SD, Gajhede M, Mirza OA, Kloverpris S, Kjaer TR, Mikkelsen JH, Boesen T, Oxvig C Nat Commun. 2022 Oct 18;13(1):6084. doi: 10.1038/s41467-022-33698-8. PMID:36257932<ref>PMID:36257932</ref>

~~Description~~:

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

[[Category: ~~Unreleased~~ Structures]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Boesen T]]

[[Category: Gajhede M]]

[[Category: Kobbero SD]]

[[Category: Mirza OA]]

[[Category: Oxvig C]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8a7d is ON HOLD  until Paper Publication
+==Partial dimer complex of PAPP-A and its inhibitor STC2==
+<StructureSection load='8a7d' size='340' side='right'caption='[[8a7d]], [[Resolution|resolution]] 3.06&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8a7d]] 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=8A7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A7D FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=8a7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a7d OCA], [https://pdbe.org/8a7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a7d RCSB], [https://www.ebi.ac.uk/pdbsum/8a7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a7d ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PAPP1_HUMAN PAPP1_HUMAN] Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is slightly inhibited by the presence of IGF.<ref>PMID:10077652</ref> <ref>PMID:10913121</ref> <ref>PMID:11522292</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The metzincin metalloproteinase PAPP-A plays a key role in the regulation of insulin-like growth factor (IGF) signaling by specific cleavage of inhibitory IGF binding proteins (IGFBPs). Using single-particle cryo-electron microscopy (cryo-EM), we here report the structure of PAPP-A in complex with its endogenous inhibitor, stanniocalcin-2 (STC2), neither of which have been reported before. The highest resolution (3.1 A) was obtained for the STC2 subunit and the N-terminal approximately 1000 residues of the PAPP-A subunit. The 500 kDa 2:2 PAPP-A.STC2 complex is a flexible multidomain ensemble with numerous interdomain contacts. In particular, a specific disulfide bond between the subunits of STC2 and PAPP-A prevents dissociation, and interactions between STC2 and a module located in the very C-terminal end of the PAPP-A subunit prevent binding of its main substrate, IGFBP-4. While devoid of activity towards IGFBP-4, the active site cleft of the catalytic domain is accessible in the inhibited PAPP-A.STC2 complex, as shown by its ability to hydrolyze a synthetic peptide derived from IGFBP-4. Relevant to multiple human pathologies, this unusual mechanism of proteolytic inhibition may support the development of specific pharmaceutical agents, by which IGF signaling can be indirectly modulated.
-Authors:
+Structure of the proteolytic enzyme PAPP-A with the endogenous inhibitor stanniocalcin-2 reveals its inhibitory mechanism.,Kobbero SD, Gajhede M, Mirza OA, Kloverpris S, Kjaer TR, Mikkelsen JH, Boesen T, Oxvig C Nat Commun. 2022 Oct 18;13(1):6084. doi: 10.1038/s41467-022-33698-8. PMID:36257932<ref>PMID:36257932</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8a7d" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Boesen T]]
+[[Category: Gajhede M]]
+[[Category: Kobbero SD]]
+[[Category: Mirza OA]]
+[[Category: Oxvig C]]