A novel phosphocholine-mimetic inhibits a pro-inflammatory conformational change of C-reactive protein

ABSTRACT: C-reactive protein (CRP) is an early-stage acute phase protein and highly upregulated in response to inflammatory reactions. We recently identified a novel mechanism that leads to a conformational change from the native, functionally relatively inert, pentameric structure (pCRP) to a pentameric intermediate (pCRP*) and ultimately to the monomeric form (mCRP), both exhibiting highly pro-inflammatory effects. This transition in the inflammatory profile of CRP is mediated by binding of pCRP to activated/damaged cell membranes via exposed phosphocholine lipid head groups. We designed a tool compound as a low molecular weight CRP inhibitor using the structure of phosphocholine as a template. X-ray crystallography revealed specific binding to the phosphocholine binding pockets of pCRP. We provid

SUBMITTER: Mr. Johannes Zeller 

PROVIDER: S-SCDT-10_15252-EMMM_202216236 | biostudies-other |

REPOSITORIES: biostudies-other