1lgn

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spinqualitylabelsall models 1lgn, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

DECAMERIC DAMP COMPLEX OF HUMAN SERUM AMYLOID P COMPONENT

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Serum amyloid P component (SAP) is a glycoprotein that binds in a, calcium-dependent fashion to a variety of ligands including other, proteins, glycosaminoglycans and DNA. SAP is universally associated with, the amyloid deposits in all forms of amyloidoses including Alzheimer's, disease. Small-molecule ligands that displace SAP from amyloid fibrils and, thereby expose the fibrils to proteolytic clearance mechanisms hold, potential as drugs for the prevention and treatment of amyloidosis. We, have carried out a screen for novel SAP ligands and have identified, 2'-deoxyadenosine-5'-monophosphate (dAMP) as a ligand. The crystal, structure of the SAP-dAMP complex determined at 2.8 A resolution (R =, 0.232, R(free) = 0.252) reveals a decamer in which all interactions, between SAP pentamers are mediated by the ligand. The stability of the, decamer in solution has been demonstrated by gel filtration, chromatography. The two calcium ions of SAP are bridged by the dAMP, phosphate group and five hydrogen bonds are formed between the protein and, the ligand, including specific interactions made by the adenine base. This, mode of dAMP binding is not compatible with the nucleotide being part of, double-helical DNA. The SAP-dAMP decamer is stabilized mainly by, base-stacking of adjacent ligand molecules and possibly by electrostatic, interactions involving the dAMP phosphate groups; decamerization buries, 1000 A2 (2.6%) of the pentamer solvent-accessible surface. Ligand-induced, decamerization of SAP, which utilizes the high cooperativity of a, multiple-site interaction, may be a strategy to overcome the problems for, drug design associated with the rather modest affinities of SAP for, small-molecule ligands.

Disease

Known disease associated with this structure: Amyloidosis, secondary, susceptibility to OMIM:[104770]

About this Structure

1LGN is a Single protein structure of sequence from Homo sapiens with CA and DA as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure of a decameric complex of human serum amyloid P component with bound dAMP., Hohenester E, Hutchinson WL, Pepys MB, Wood SP, J Mol Biol. 1997 Jun 20;269(4):570-8. PMID:9217261

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