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SMALL ANGLE X-RAY SCATTERING, MOLECULAR MODELING, AND CHEMOMETRIC STUDIES FROM A THROMBIN-LIKE (LMR-47) ENZYME OF LACHESIS M. RHOMBEATA VENOM
SVTLE
Estrutura da solução
Forma proteica
Inibidores de guanidina
Inibidor de amidina
SVTLE
Solution structure
Protein shape
Guanidine inhibitors
Amidine inhibitor
Author
Affilliation
Abstract
Abstract: Introduction: Snakebite envenomation is considered a neglected tropical disease, and
SVTLEs critical elements are involved in serious coagulopathies that occur on envenoming. Although
some enzymes of this group have been structurally investigated, it is essential to characterize other
proteins to better understand their unique properties such as the Lachesis muta rhombeata 47 kDa
(Lmr-47) venom serine protease. Methods: The structure of Lmr-47 was studied in solution, using
SAXS, DLS, CD, and in silico by homology modeling. Molecular docking experiments simulated
21 competitive inhibitors. Results: At pH 8.0, Lmr-47 has an Rg of 34.5 ± 0.6 Å, Dmax of 130 Å, and
SR of 50 Å, according to DLS data. Kratky plot analysis indicates a rigid shape at pH 8.0. Conversely,
the pH variation does not change the center of mass’s intrinsic fluorescence, possibly indicating
the absence of fluorescent amino acids in the regions affected by pH variation. CD experiments
show a substantially random coiled secondary structure not affected by pH. The low-resolution
model of Lmr-47 presented a prolate elongated shape at pH 8.0. Using the 3D structure obtained
by molecular modeling, docking experiments identified five good and three suitable competitive
inhibitors. Conclusion: Together, our work provided insights into the structure of the Lmr-47 and
identified inhibitors that may enhance our understanding of thrombin-like family proteins.
Keywords in Portuguese
Lachelis m. rhombeata; protease serinaSVTLE
Estrutura da solução
Forma proteica
Inibidores de guanidina
Inibidor de amidina
Keywords
Lachelis m. rhombeata; serine proteaseSVTLE
Solution structure
Protein shape
Guanidine inhibitors
Amidine inhibitor
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