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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Detection of the Apo-B,E-binding Site of Low DensityLipoprotein ReceptorIrina V. Shutova and Vladimir P. GolubovichInstitute of Bioorganic Chemistry of the National Academy of Sciences of Belarus,Minsk, Kuprevich str. 5/2, 220141, Belarus; e-mail: shutova2001@mail.ruIntroductionApolipoproteins Apo-E and Apo-B100 play an important role in the development of thecardiovascular diseases. Their selective elimination from patient’s serum is one of themethods of the treatment and prophylaxis of cardiovascular disease such as myocardialinfarction, stroke and atherosclerosis. These proteins bind with one receptor – low densitylipoprotein receptor (LDLR). Detection of the Apo-B,E-binding site of LDLR anddesigning its low-molecular analogs can result in the making of new medical adsorbentsand therapeutic agents.Low density lipoprotein receptor is a protein with known 3D structure and consists ofseveral independent domains. Ligand-binding domain of LDLR is placed in N-terminal ofmolecule and consists of 7 repeats with 50% homology. Apo-E binds with repeat 5 ofLDLR. Apo-B100 has two binding regions: one of them binds with repeat 4 of LDLR andanother binds with repeat 5 of LDLR and has high homology with receptor-binding regionof Apo-E. Repeat 5 of LDLR presumably has one Apo-B,E-binding site and both Apo-Eand Apo-B100 competitively bind with it [1]. The aim of our study was to detect theApo-B,E-binding site of LDLR.Results and DiscussionDetection of the Apo-B,E-binding site of LDLR was carried out by a program designed byus. As is known, the specific protein binding sites usually are placed in the cavities orconvexities on protein surfaces [2]. Therefore, the detection of the structural features ofprotein surfaces – cavities and convexities, is often the first stage of the functional analysisof proteins. The next step is the investigation of the detected structural features. Mostwidely used methods are those in which the cavities are ranked by area and/or by volume.In this case the cavities with rank one refer to potential binding sites [3-5]. It is known thatthe binding sites of proteins usually form charged regions or have well-markedhydrophobic nature [2]. So for the detection of potential binding sites of proteins weconsider it expedient to investigate the hydrophobic properties and charge distribution inthe cavities and on protein surfaces.We have designed the program for prediction of potential binding sites of proteins(Figure 1). This program consists of three modules which allow us to build the molecularprotein surfaces (module 1); to detect and to rank the cavities – structural features ofprotein surfaces (module 2); and to carry out the analysis of hydrophobic areas and chargedistribution on protein surfaces (module 3).Import of the3D structures,PDB-typeModule 1The building of themolecular protein surfacesMolecular protein surface,PDB-typeModule 2The detection and ranking ofthe cavities on protein surfaceCavities on protein surface,PDB-typeModule 3The analysis of thehydrophobic areas and chargedistribution in the cavities andon protein surfacesPotential bindingsitesFig. 1. Scheme of the program.272