Interactions between dodecamers of hyaluronan and hyaluronan-like molecules with TSG-6 protein

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F70883521%3A28110%2F18%3A63520159" target="_blank" >RIV/70883521:28110/18:63520159 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Interactions between dodecamers of hyaluronan and hyaluronan-like molecules with TSG-6 protein

Original language description

Hyaluronan (HA) is a linear non-sulfated polysaccharide of natural origin, which contains disaccharide repeats of D-glucuronic acid and N-acetyl-D-glucosamine. HA is found pervasively in the extracellular matrix (ECM), where it can noncovalently bind to a variety of proteins and influence their functions. The biological functions of HA depend on the molecular weight of its chain [1]. One of the modified HA, hyaluronan neutral analog (GlcHA), where recurrent monosaccharide units of D-glucuronic acid from HA were substituted by D-glucose, can be promising biocompatible material for the design of drugs [2]. Tumor necrosis factor stimulated gene-6 (TSG-6) is a hyaluronan-binding protein (hyaladherin) that is essential for stabilizing and remodeling the ECM. This protein consists mainly contiguous N-terminal Link and C-terminal CUB domains, it is a potential biomarker of diseases associated with carcinogenesis, which is a possible target for drug delivery [3]. In this study, we simulated the binding of hyaluronan dodecamer (HA12) and its neutral analog (GlcHA12) to the Link domain of TSG-6 protein by using a molecular dynamics method. All simulations were performed in GROMACS software package (version 5.1.2) using the CHARMM36 all-atom force field at two different concentrations of NaCl solutions at 300 K under an NVT conditions. The ability of binding both HA12 and GlcHA12 seems to be facilitated by the high occurrence of the amino acids capable of hydrogen-bond formation, especially lysines and arginines, and the flexibility of the Link-domain structure allowing the protein to adapt to the ligand shape. It suggested the potentiality of designing synthetic ligands of protein receptors with regard to their possible pharmaceutical applications.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10610 - Biophysics

Project

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Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů