Evidence map›Paper›PMID 24083244›Full record

ArticleBioMed research international2013

Comparative analyses of the β-tubulin gene and molecular modeling reveal molecular insight into the colchicine resistance in kinetoplastids organisms.

Luis Luis, María Luisa Serrano, Mariana Hidalgo, Alexis Mendoza-León

Open access · hybridAbstract readComparative Study
In one paragraph

Article in BioMed research international, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 21 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Luis LuisLaboratorio de Bioquímica y Biología Molecular de Parásitos, Instituto de Biología Experimental (IBE), Facultad de Ciencias, Universidad Central de Venezuela (UCV), Caracas 1041A, Venezuela.
María Luisa Serrano
Mariana Hidalgo
Alexis Mendoza-León
Central University of Venezuela · VEInstituto Venezolano de Investigaciones Científicas · VE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Differential susceptibility to microtubule agents has been demonstrated between mammalian cells and kinetoplastid organisms such as Leishmania spp. and Trypanosoma spp. The aims of this study were to identify and characterize the architecture of the putative colchicine binding site of Leishmania spp. and investigate the molecular basis of colchicine resistance. We cloned and sequenced the β-tubulin gene of Leishmania (Viannia) guyanensis and established the theoretical 3D model of the protein, using the crystallographic structure of the bovine protein as template. We identified mutations on the Leishmania β-tubulin gene sequences on regions related to the putative colchicine-binding pocket, which generate amino acid substitutions and changes in the topology of this region, blocking the access of colchicine. The same mutations were found in the β-tubulin sequence of kinetoplastid organisms such as Trypanosoma cruzi, T. brucei, and T. evansi. Using molecular modelling approaches, we demonstrated that conformational changes include an elongation and torsion of an α-helix structure and displacement to the inside of the pocket of one β-sheet that hinders access of colchicine. We propose that kinetoplastid organisms show resistance to colchicine due to amino acids substitutions that generate structural changes in the putative colchicine-binding domain, which prevent colchicine access.

Indexed as

Models, MolecularAmino Acid SequenceAmino Acid SubstitutionAnimalsBinding SitesCattleColchicineDrug ResistanceKinetoplastidaLeishmaniaMolecular Sequence DataProtein BindingProtein Structure, SecondarySequence AlignmentTubulinColchicineTubulin

Identifiers

PMID24083244
PMCPMC3780476
OpenAlexW2036732182

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.