8a7e: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
The | ==PAPP-A dimer in complex with its inhibitor STC2== | ||
<StructureSection load='8a7e' size='340' side='right'caption='[[8a7e]], [[Resolution|resolution]] 5.02Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8a7e]] is a 4 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=8A7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8A7E 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=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=8a7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8a7e OCA], [https://pdbe.org/8a7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8a7e RCSB], [https://www.ebi.ac.uk/pdbsum/8a7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8a7e ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/STC2_HUMAN STC2_HUMAN] Has an anti-hypocalcemic action on calcium and phosphate homeostasis. | |||
<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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8a7e" 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]] | |||
Revision as of 07:23, 3 November 2022
PAPP-A dimer in complex with its inhibitor STC2
| ||||||||||||
