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Stratification of chondroitin sulfate binding sites in 3D-model of bovine testicular hyaluronidase and effective size of glycosaminoglycan coat of the modified protein

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Abstract

A 3D-model of bovine testicular hyaluronidase (BTH) was constructed based on established tertiary structure of human hyaluronidase Hyal1 using a molecular homological modeling method in silico. The analysis of the BTH 3D-model demonstrated lysine residue stratification during enzyme modification. The 3D-model of chondroitin sulfate (CHS)-modified hyaluronidase (BTH-CHS) was obtained by modeling covalent binding of lysine residues with benzoquinone-activated CHS. The degree of enzyme modification and the length of CHS chains were varied during 3D modeling. The importance of deep BTH modification degree for the formation of active and stable enzyme derivatives was shown, as determined earlier experimentally. The effective size of the CHS coat for productive BTH modification was confirmed. It is theoretically achieved at the increase in molecular mass of BTH-CHS derivative to approximately 140–180 kDa and can be practically obtained, according to experimental data, using CHS of different molecular mass (30–50 as well as 120–140 kDa).

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Abbreviations

BTH:

bovine testicular hyaluronidase

CHS:

chondroitin sulfate

3D:

spatial/three-dimensional/tertiary protein structure

EGF:

epidermal growth factor

GCU:

glucuronic acid

Hyal1:

human hyaluronidase

NAG:

N-acetylglucosamine

RMS:

root mean square deviation of model Cα-atoms from prototype Cα-atoms

TNBS:

trinitrobenzenesulfonic acid

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Authors and Affiliations

  1. Institute of Experimental Cardiology, Russian Cardiology Research and Production Complex, 3-ya Cherepkovskaya ul. 15A, 121552, Moscow, Russia

    A. V. Maksimenko, A. D. Turashev & R. S. Beabealashvili

Authors
  1. A. V. Maksimenko
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  2. A. D. Turashev
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  3. R. S. Beabealashvili
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Correspondence to A. V. Maksimenko.

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Original Russian Text © A. V. Maksimenko, A. D. Turashev, R. S. Beabealashvili, 2015, published in Biokhimiya, 2015, Vol. 80, No. 3, pp. 348–357.

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Maksimenko, A.V., Turashev, A.D. & Beabealashvili, R.S. Stratification of chondroitin sulfate binding sites in 3D-model of bovine testicular hyaluronidase and effective size of glycosaminoglycan coat of the modified protein. Biochemistry Moscow 80, 284–295 (2015). https://doi.org/10.1134/S0006297915030049

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  • DOI: https://doi.org/10.1134/S0006297915030049

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