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| | <StructureSection load='6rx7' size='340' side='right'caption='[[6rx7]], [[Resolution|resolution]] 1.63Å' scene=''> | | <StructureSection load='6rx7' size='340' side='right'caption='[[6rx7]], [[Resolution|resolution]] 1.63Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6rx7]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RX7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6RX7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6rx7]] 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=6RX7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RX7 FirstGlance]. <br> |
| - | </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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.63Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LPA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6rx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rx7 OCA], [http://pdbe.org/6rx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rx7 RCSB], [http://www.ebi.ac.uk/pdbsum/6rx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rx7 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=6rx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rx7 OCA], [https://pdbe.org/6rx7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rx7 RCSB], [https://www.ebi.ac.uk/pdbsum/6rx7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rx7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/APOA_HUMAN APOA_HUMAN]] Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for megalin/Gp 330.<ref>PMID:2531657</ref> | + | [https://www.uniprot.org/uniprot/APOA_HUMAN APOA_HUMAN] Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for megalin/Gp 330.<ref>PMID:2531657</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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Maggi, M]] | + | [[Category: Maggi M]] |
| - | [[Category: Santonastaso, A]] | + | [[Category: Santonastaso A]] |
| - | [[Category: Scotti, C]] | + | [[Category: Scotti C]] |
| - | [[Category: Kiv-2]]
| + | |
| - | [[Category: Kringle iv type 2]]
| + | |
| - | [[Category: Lipid transport]]
| + | |
| Structural highlights
Function
APOA_HUMAN Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for megalin/Gp 330.[1]
Publication Abstract from PubMed
Lipoprotein (a) [Lp(a)] is characterized by an LDL-like composition in terms of lipids and apoB100, and by one copy of a unique glycoprotein, apo(a). The apo(a) structure is mainly based on the repetition of tandem kringle domains with high homology to plasminogen kringles 4 and 5. Among them, kringle IV type 2 (KIV-2) is present in a highly variable number of genetically encoded repeats, whose length is inversely related to Lp(a) plasma concentration and cardiovascular risk. Despite it being the major component of apo(a), the actual function of KIV-2 is still unclear. Here, we describe the first high-resolution crystallographic structure of this domain. It shows a general fold very similar to other KIV domains with high and intermediate affinity for the lysine analog, epsilon-aminocaproic acid. Interestingly, KIV-2 presents a lysine binding site (LBS) with a unique shape and charge distribution. KIV-2 affinity for predicted small molecule binders was found to be negligible in surface plasmon resonance experiments; and with the LBS being nonfunctional, we propose to rename it "pseudo-LBS". Further investigation of the protein by computational small-molecule docking allowed us to identify a possible heparin-binding site away from the LBS, which was confirmed by specific reverse charge mutations abolishing heparin binding. This study opens new possibilities to define the pathogenesis of Lp(a)-related diseases and to facilitate the design of specific therapeutic drugs.
High resolution structure of human apolipoprotein (a) kringle IV type 2: beyond the lysine binding site.,Santonastaso A, Maggi M, De Jonge H, Scotti C J Lipid Res. 2020 Dec;61(12):1687-1696. doi: 10.1194/jlr.RA120001023. Epub 2020, Sep 9. PMID:32907988[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Salonen EM, Jauhiainen M, Zardi L, Vaheri A, Ehnholm C. Lipoprotein(a) binds to fibronectin and has serine proteinase activity capable of cleaving it. EMBO J. 1989 Dec 20;8(13):4035-40. PMID:2531657
- ↑ Santonastaso A, Maggi M, De Jonge H, Scotti C. High resolution structure of human apolipoprotein (a) kringle IV type 2: beyond the lysine binding site. J Lipid Res. 2020 Dec;61(12):1687-1696. doi: 10.1194/jlr.RA120001023. Epub 2020, Sep 9. PMID:32907988 doi:http://dx.doi.org/10.1194/jlr.RA120001023
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