Serum amyloid P-component
From Proteopedia
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- | <StructureSection load=' | + | <StructureSection load='1lgn' size='340' side='right' caption='Structure of human pentameric SAP (green, grey, pink, yellow, magenta) complex with AMP and Ca+2 ions (green) (PDB code [[1lgn]])' scene='87/875651/Cv/1'> |
== Function == | == Function == | ||
- | '''Serum amyloid P-component''' (SAP) is a plasma protein and is the precursor of amyloid P-component which is constituent of deposits in amyloidosis and Alzheimer disease<ref>PMID:8202534</ref>. | + | '''Serum amyloid P-component''' (SAP) is a plasma protein and is the precursor of amyloid P-component which is constituent of deposits in amyloidosis and Alzheimer disease<ref>PMID:8202534</ref>. SAP binds in a calcium-dependent fashion to a variety of ligands. |
== Relevance == | == Relevance == | ||
- | Mutations in SAP affect the aggregation of mutated lysozyme which cause amyloidosis. The inhibition of SAP binding to amyloid fibrils is a therapeutic target in some serious human diseases<ref>PMID:26176329</ref>. | + | Mutations in SAP affect the aggregation of mutated lysozyme which cause amyloidosis. The inhibition of SAP binding to amyloid fibrils is a therapeutic target in some serious human diseases<ref>PMID:26176329</ref>. Small molecule ligands can displace SAP from amyloid fibrils and can provide therapeutic treatment of amyloidosis. |
== Structural highlights == | == Structural highlights == | ||
- | <scene name='87/ | + | <scene name='87/875651/Cv/5'>The 3D structure of a complex of SAP with the small molecule ligand AMP</scene> shows the nucleotide phosphate group bridging two Ca+2 ions and forming hydrogen bonds to Asn, Gln and Try residues of SAP <ref>PMID:9217261</ref>. <scene name='87/875651/Cv/6'>Ca coordination sites</scene>. |
</StructureSection> | </StructureSection> |
Current revision
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3D Structures of serum amyloid P-component
Updated on 22-February-2021
1sac – hSAP – human
2a3w, 2a3x, 2a3y – hSAP + bivalent ligand
1gyk – hSAP + galactose derivative
1lgn – hSAP + AMP derivative
2w08 – hSAP + Thr derivative
4avs, 4avt, 4avv, 4ayu – hSAP + Pro derivative
3kqr – hSAP + ethanolamine derivative
3d5o – hSAP + Igg Fc receptor
1qtj – SAP – Limulus polyphemus
References
- ↑ Pepys MB, Rademacher TW, Amatayakul-Chantler S, Williams P, Noble GE, Hutchinson WL, Hawkins PN, Nelson SR, Gallimore JR, Herbert J, et al.. Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5602-6. doi: 10.1073/pnas.91.12.5602. PMID:8202534 doi:http://dx.doi.org/10.1073/pnas.91.12.5602
- ↑ Richards DB, Cookson LM, Berges AC, Barton SV, Lane T, Ritter JM, Fontana M, Moon JC, Pinzani M, Gillmore JD, Hawkins PN, Pepys MB. Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component. N Engl J Med. 2015 Sep 17;373(12):1106-14. doi: 10.1056/NEJMoa1504942. Epub 2015 , Jul 15. PMID:26176329 doi:http://dx.doi.org/10.1056/NEJMoa1504942
- ↑ Hohenester E, Hutchinson WL, Pepys MB, Wood SP. Crystal structure of a decameric complex of human serum amyloid P component with bound dAMP. J Mol Biol. 1997 Jun 20;269(4):570-8. PMID:9217261 doi:10.1006/jmbi.1997.1075