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Identifying potential drug targets in the kinomes of two monogenean species

V. H. Caña-Bozada
V. H. Caña-Bozada
, 
C. Ovando-Vázquez
C. Ovando-Vázquez
, 
L. C. Flores-Méndez
L. C. Flores-Méndez
, 
J. M. Martínez-Brown
J. M. Martínez-Brown
 oraz 
F. N. Morales-Serna
F. N. Morales-Serna
   | 16 lip 2024
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Data publikacji: 16 lip 2024
Zakres stron: 142 - 150
Otrzymano: 12 wrz 2023
Przyjęty: 24 maj 2024
DOI: https://doi.org/10.2478/helm-2024-0020
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© 2024 V. H. Caña-Bozada et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig. 1.

Bioinformatic pipeline for the identification, classification, and selection of potential drug targets. A) Pipeline for the identification and classification of monogenean kinases. B) Classification of protein kinases. C) Pipeline used for the identification of drug targets. D) Pipeline used for the prioritization of monogenean drug targets (MDTs). ePKs, eukaryotic protein kinases; aPKs, atypical protein kinases; AGC, cAMP-dependent protein kinase/protein kinase G/protein kinase C extended family; CAMK, calcium/calmodulin-dependent kinase; CK1, cell kinase 1; CMGC, cyclin-dependent kinases and other close relatives; PKL, protein kinase-like; RGC, receptor guanylate cyclase; STE, MAP kinase cascade kinases; TK, protein tyrosine kinase; TKL, tyrosine kinase-like.
Bioinformatic pipeline for the identification, classification, and selection of potential drug targets. A) Pipeline for the identification and classification of monogenean kinases. B) Classification of protein kinases. C) Pipeline used for the identification of drug targets. D) Pipeline used for the prioritization of monogenean drug targets (MDTs). ePKs, eukaryotic protein kinases; aPKs, atypical protein kinases; AGC, cAMP-dependent protein kinase/protein kinase G/protein kinase C extended family; CAMK, calcium/calmodulin-dependent kinase; CK1, cell kinase 1; CMGC, cyclin-dependent kinases and other close relatives; PKL, protein kinase-like; RGC, receptor guanylate cyclase; STE, MAP kinase cascade kinases; TK, protein tyrosine kinase; TKL, tyrosine kinase-like.

The highest binding affinities (≤ −9.0 kcal/mol) obtained from molecular docking using a set of FDA-approved drugs.

Drug Species Receptor id Binding affinity (kcal/mol)
Dihydroergotaminea S. longicornis Contig773.p1 and Contig772.p1 −9.7
Lomitapideb R. viridisi TRINITY_DN1044_c0_g2_i2.p2 −9.5
Dihydroergotaminea R. viridisi TRINITY_DN1044_c0_g2_i2.p2 −9.4
Ergotaminec S. longicornis Contig773.p1 and Contig772.p1 −9.2
Bicalutamided R. viridisi Contig130.p1 −9.1
Piroxicame R. viridisi TRINITY_DN1044_c0_g2_i2.p2 −9.0
Suvorexantf R. viridisi TRINITY_DN1044_c0_g2_i2.p2 −9.0

Classification of kinases in various platyhelminths.

Group AGC CAMK CK1 CMGC PKL Other RGC RGC/CAMK STE TK TKL Unknown Atypical Total general
Monogenea R. viridisi 29 17 10 30 5 25 2 - 13 19 9 - 1 160
S. longicornis 32 27 11 34 4 29 2 - 13 26 13 - 2 193
Cestoda E. multilocularis 43 35 11 44 - 30 5 - 25 46 26 - - 265
E. granulosus 41 35 11 43 - 30 5 - 24 42 22 - - 253
T. solium 56 36 12 61 - 37 11 1 28 45 23 - - 310
H. microstoma 48 33 13 64 - 30 6 - 28 33 18 - - 273
Trematoda S. mansoni 34 38 9 44 - 39 3 - 27 34 19 5 - 252
S. haematobium 39 41 9 51 4 40 3 - 27 31 20 4 - 269
S. japonicum 27 33 8 41 6 35 4 - 23 31 13 - 1 222
F. gigantica 44 55 13 66 - 45 0 - 35 34 16 - - 308
F. buski 33 42 10 47 - 40 1 - 23 39 15 - - 250

Kinases of Rhabdosynochus viridisi and Scutogyrus longicornis predicted to be monogenean drug targets (MDTs).

Species ID Classification (group/family/subfamily) Priority for molecular docking ***
R. viridisi Contig3487.p1 (CK1/CK1/CK1-A) -
R. viridisi Contig474.p1 (AGC) -
R. viridisi Contig130.p1 (AGC/RSK/RSKp70) 1**
R. viridisi TRINITY_DN128_c1_g2_i2.p1 (TK/Ack) -
R. viridisi TRINITY_DN430_c0_g1_i4.p1 (TK/Fer) -
R. viridisi Contig2641.p1 (AGC/PKG) -
R. viridisi TRINITY_DN4663_c0_g2_i1.p1a (CAMK/CAMKL/BRSK) -
R. viridisi Contig4408.p1 (CAMK/MLCK) -
R. viridisi Contig5219.p1 (CMGC/GSK) -
R. viridisi TRINITY_DN1044_c0_g2_i2.p2 (STE/STE11/MEKK1) 3*
R. viridisi Contig3286.p1 (CAMK/CAMKL/MARK) -
S. longicornis Contig1825.p1 (TK/Ack) -
S. longicornis TRINITY_DN2502_c0_g3_i3__g.25108 (TK) -
S. longicornis TRINITY_DN770_c0_g1_i4__g.58217 (TK/Fer) -
S. longicornis Contig3492.p1 (AGC/PKG) -
S. longicornis TRINITY_DN1812_c0_g1_i2__g.5503 (AGC/RSK/RSKp70) 1*
S. longicornis TRINITY_DN7486_c0_g6_i1__g.37596 (CAMK/MLCK) -
S. longicornis TRINITY_DN1065_c0_g1_i1__g.51110 (CMGC/GSK) -
S. longicornis TRINITY_DN14095_c0_g1_i1__g.60752 (CK1/CK1/CK1-A) -
S. longicornis Contig772.p1a (CAMK/CAMKL/BRSK) 2**
S. longicornis Contig773.p1a (CAMK/CAMKL/BRSK) 2**
S. longicornis Contig3764.p1 (CAMK/CAMKL/MARK) -
eISSN:
1336-9083
Język:
Angielski
Częstotliwość wydawania:
4 razy w roku
Dziedziny czasopisma:
Life Sciences, Zoology, Ecology, other, Medicine, Clinical Medicine, Microbiology, Virology and Infection Epidemiology
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