Homology modeling and docking of AahII-Nanobody complexes reveal the epitope binding site on AahII scorpion toxin

Journal Article · Thu Feb 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.01.036· OSTI ID:23137352

Ksouri, Ayoub ^[1]; Ghedira, Kais ^[2]; Ben Abderrazek, Rahma ^[1]; Shankar, B.A. Gowri ^[3]; Benkahla, Alia ^[2]; Bishop, Ozlem Tastan ^[4]; Bouhaouala-Zahar, Balkiss ^[1]

---

1. Laboratoire des Venins et Molécules Thérapeutiques, Institut Pasteur de Tunis, 13 Place Pasteur, BP74, Tunis Belvédère- University of Tunis El Manar (Tunisia)
2. Laboratory of BioInformatics, Biomathematics and Biostatistics (BIMS), Institut Pasteur de Tunis, 13 Place Pasteur, BP74, Tunis Belvédère- University of Tunis El Manar, Tunis (Tunisia)
3. Laboratory for Venom Peptidomics and Molecular Simulation Bannari Institute of Technology, Alathukombai, Post Sathyamangalam, 638 401, Erode District, Tamil Nadu (India)
4. Research Unit in Bioinformatics (RUBi), Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140 (South Africa)

Highlights: • AahII specific nanobodies share common CDRs sequence patterns. • Residues forming sequences' pattern interact specifically with AahII. • CDR1 Tyr27, Tyr29 and Ser30 polar residues are involved in AahII neutralization. • Interacting AahII Arg62/NbAahII10 CDR3 Asp112 charged residues are crucial. • AahII-NbAahII10 trapping involves a distinct toxin 3D orientation. Scorpion envenoming and its treatment is a public health problem in many parts of the world due to highly toxic venom polypeptides diffusing rapidly within the body of severely envenomed victims. Recently, 38 AahII-specific Nanobody sequences (Nbs) were retrieved from which the performance of NbAahII10 nanobody candidate, to neutralize the most poisonous venom compound namely AahII acting on sodium channels, was established. Herein, structural computational approach is conducted to elucidate the Nb-AahII interactions that support the biological characteristics, using Nb multiple sequence alignment (MSA) followed by modeling and molecular docking investigations (RosettaAntibody, ZDOCK software tools). Sequence and structural analysis showed two dissimilar residues of NbAahII10 CDR1 (Tyr27 and Tyr29) and an inserted polar residue Ser30 that appear to play an important role. Indeed, CDR3 region of NbAahII10 is characterized by a specific Met104 and two negatively charged residues Asp115 and Asp117. Complex dockings reveal that NbAahII17 and NbAahII38 share one common binding site on the surface of the AahII toxin divergent from the NbAahII10 one's. At least, a couple of NbAahII10 – AahII residue interactions (Gln38 – Asn44 and Arg62, His64, respectively) are mainly involved in the toxic AahII binding site. Altogether, this study gives valuable insights in the design and development of next generation of antivenom.

• OSTI ID: 23137352
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 496; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
POLYPEPTIDES
PUBLIC HEALTH
SCORPIONS
TOXICITY
TOXINS
VENOMS