The Rational Investigation of Anti-Cancer Peptide Specificity using the Knob-Socket Model - CORE CORE Services Services overviewExplore all CORE services Access to raw data API Dataset FastSync Content discovery Recommender Discovery Managing content Repository dashboard Packages Repository edition About About us Our mission Team Blog FAQs Contact us The Rational Investigation of Anti-Cancer Peptide Specificity using the Knob-Socket Model Authors Shivarni Patel Publication date January 1, 2017 Publisher Scholarly Commons Abstract Cancer has been a pervasive and deadly problem for many years. No treatments have been developed that effectively destroy cancer cells while also keeping healthy cells safe. In this work, the knob-socket construct is used to analyze two systems involved in cancer pathways, the PDZ domain and the Bcl-BH3 complex. Application of the knob-socket model in mapping the packing surface topology (PST) allows a direct analysis of the residue groups important for peptide specificity and affinity in both of these systems. PDZ domains are regulatory proteins that bind the C-terminus of peptides involved in the signaling pathway of cancer progression. The domain includes five -strands, two -helices, and six coils/turns. In this study, the PST of all eight solved crystal structures of T-cell lymphoma invasion and metastasis 1 (Tiam1) PDZ domains are mapped to reveal details of ligand-domain binding pockets and packing interactions. Four main interactions were identified in the comparison of the PST maps and a consensus sequence was calculated using knob-socket interaction data. In the case of the Bcl-BH3 complex, binding of these two proteins prevents an unhealthy cell from undergoing apoptosis. In the knob-socket mapped protein-ligand interactions, the helical ligand consists of 8 to 10 residues that specifically interact with four helices on the binding protein: the N-terminus of Helix2, the main bodies of Helix3 and Helix4 and the C-terminus of Helix5. Among all of the interactions that were analyzed, there were three amino acids from the ligand, glycine, leucine, and isoleucine, that always packed into the hydrophobic groove that is key for ligand recognition. By using knob-socket analysis to map quaternary packing structure, it was possible to identify the quaternary-level protein interactions that define ligand specificity and binding strength. From this analysis, possible protein mimetics can be developed that could be used as cancer treatments text Biochemistry Bcl-2 Domain Knob-Socket Model PDZ Domain Protein Folding Chemistry Pharmacy and Pharmaceutical Sciences Similar works Full text Pacific McGeorge School of LawFull text is not available oai:scholarlycommons.pacific.edu:uop_etds-3983 Last time updated on 12/30/2019 This paper was published in Pacific McGeorge School of Law. Having an issue? Is data on this page outdated, violates copyrights or anything else? Report the problem now and we will take corresponding actions after reviewing your request. Report CORE is not-for-profit service delivered by the Open University and Jisc. Product Services Data providers Communities Terms Organisation About us Mission Team Blog Support FAQs Contact us Writing about CORE? Discover our research outputs and cite our work. COREAccessabilityCookiesPrivacy
