International Journal of Infertility & Fetal Medicine

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VOLUME 13 , ISSUE 3 ( September-December, 2022 ) > List of Articles


Structure Prediction and Binding Site Analysis of Human Sperm Hyaluronidases

Prasanth Gunasekaran, Madhukar Hemamalini, Rajakannan Venkatachalam

Keywords : Acrosome reaction, Homology modeling, Hyaluronic acid binding, Molecular docking, Sperm hyaluronidases

Citation Information : Gunasekaran P, Hemamalini M, Venkatachalam R. Structure Prediction and Binding Site Analysis of Human Sperm Hyaluronidases. Int J Infertil Fetal Med 2022; 13 (3):96-100.

DOI: 10.5005/jp-journals-10016-1280

License: CC BY-NC 4.0

Published Online: 29-12-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Background: Sperm cell hyaluronidases are important class of enzymes which play a prominent role in hydrolyzing hyaluronan during sperm penetration through the layer of cumulus and zona pellucida of egg. Clinically sperm hyaluronidases play important role in analyzing sperm binding quality during IVF treatments by hyaluronan binding assay. The functions of sperm hyaluronidases such as penetrating the hyaluronan matrix of cumulus layer, inducing hyaluronan-based acrosome reaction were directly related to substrate binding efficiency of these enzymes. Though hyaluronidases were confirmed to play the hyaluronan hydrolyzing role in fertilization, there is no structural evidence to prove their difference in molecular weight-based substrate specificity and their multifunctional activity in fertilization. This work presents the evidence on the binding modes of hyaluronan with sperm cell hyaluronidases using homology modeling and molecular docking methods. Materials and methods: The different isoforms of human sperm hyaluronidases were modelled using human hyaluronidase 1 (PDB code 2PE4) and the optimized structure of hyaluronan from the crystal structure of bee venom hyaluronidase complexed with HA tetramer (PDB Code: 1vcz) was docked using AUTODOCK TOOLS. The results are evaluated based on the complex binding energy and interaction with substrate binding residues. Results: The molecular docking results confirm the binding of hyaluronan with HYAL-2 in the deep substrate-binding groove, which was absent in HYAL-3 and HPH-20 hyaluronan complex. The binding of hyaluronan with HPH-20 and HYAL-3, involved in neutral-active domain and residues present in perpendicular beta sheets. The binding mode of HYAL-2 is more on acid-active region of the enzyme which was considered to induce hyaluronan-dependent cell signaling and AR activation. Conclusion: The results conclude that the substrate accommodation pattern of HYAL-2 was differed from HYAL-3 and HPH-20 where the acid active domain of HYAL-2 may predominantly involve in AR activation and zona pellucida penetration apart from cumulus HA degradation.

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