Abstract：
:Spreading of the multidrug-resistant (MDR) strains of the one of the most harmful pathogen Mycobacterium tuberculosis (Mtb) generates the need for new effective drugs. SQ109 showed activity against resistant Mtb and already advanced to Phase II/III clinical trials. Fast SQ109 degradation is attributed to the human liver Cytochrome P450s (CYPs). However, no information is available about interactions of the drug with Mtb CYPs. Here, we show that Mtb CYP124, previously assigned as a methyl-branched lipid monooxygenase, binds and hydroxylates SQ109 in vitro. A 1.25 Å-resolution crystal structure of the CYP124-SQ109 complex unambiguously shows two conformations of the drug, both positioned for hydroxylation of the ω-methyl group in the trans position. The hydroxylated SQ109 presumably forms stabilizing H-bonds with its target, Mycobacterial membrane protein Large 3 (MmpL3). We anticipate that Mtb CYPs could function as analogs of drug-metabolizing human CYPs affecting pharmacokinetics and pharmacodynamics of antitubercular (anti-TB) drugs.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Bukhdruker S,Varaksa T,Grabovec I,Marin E,Shabunya P,Kadukova M,Grudinin S,Kavaleuski A,Gusach A,Gilep A,Borshchevskiy V,Strushkevich Ndoi
10.3390/ijms21207683subject
Has Abstractpub_date
2020-10-16 00:00:00issue
20issn
1422-0067pii
ijms21207683journal_volume
21pub_type
杂志文章abstract：:The Gram-negative Campylobacter jejuni is a major cause of foodborne gastroenteritis in humans worldwide. The cytotoxic effects of Campylobacter have been mainly ascribed to the actions of the cytolethal distending toxin (CDT): it is mandatory to put in evidence risk factors for sequela development, such as reactive a...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21062207
更新日期：2020-03-23 00:00:00
abstract：:Phototropin2 (phot2) is a blue-light (BL) receptor protein that regulates the BL-dependent activities of plants for efficient photosynthesis. Phot2 is composed of two light-oxygen-voltage sensing domains (LOV1 and LOV2) to absorb BL, and a kinase domain. Photo-activated LOV domains, especially LOV2, play a major role ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21186638
更新日期：2020-09-10 00:00:00
abstract：:Ketamine, a multimodal anesthetic drug, has become increasingly popular in the treatment of pain following traumatic injury as well as treatment-resistant major depressive disorders. However, the psychological impact of this dissociative medication on the development of stress-related disorders such as post-traumatic ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21197173
更新日期：2020-09-28 00:00:00
abstract：:The homeostatic control of lipid metabolism is essential for many fundamental physiological processes. A deep understanding of its regulatory mechanisms is pivotal to unravel prospective physiopathological factors and to identify novel molecular targets that could be employed to design promising therapies in the manag...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21041297
更新日期：2020-02-14 00:00:00
abstract：:Bioelectrochemical systems (BES) are groups of bioelectrochemical technologies and platforms that could facilitate versatile environmental and biological applications. The performance of BES is mainly determined by the key process of electron transfer at the bacteria and electrode interface, which is known as extracel...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms18010090
更新日期：2017-01-04 00:00:00
abstract：:The interactions of plants with environment and insects are bi-directional and dynamic. Consequently, a myriad of mechanisms has evolved to engage organisms in different types of interactions. These interactions can be mediated by allelochemicals known as volatile organic compounds (VOCs) which include volatile terpen...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21197382
更新日期：2020-10-06 00:00:00
abstract：:Molecular defects in type 1 facioscapulohumeral muscular dystrophy (FSHD) are caused by a heterozygous contraction of the D4Z4 repeat array from 1 to 10 repeat units (RUs) on 4q35. This study compared (1) the phenotype and severity of FSHD1 between patients carrying 6-8 vs. 9-10 RUs, (2) the amount of methylation in d...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21062221
更新日期：2020-03-23 00:00:00
abstract：:In order to generate an antibody against a small hapten molecule, the hapten is cross-linked with carrier protein to make it immunogenic. In this study, the hapten (Fumonisin B(1), FB(1)) was coupled to ovalbumin (OVA) and bovine serum albumin (BSA), respectively by a short cross-linker reagent (glutaraldehyde, GA). T...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms13010084
更新日期：2012-01-01 00:00:00
abstract：:A psychrotolerant bacterium, strain T-3 (identified as Psychrobacter piscatorii), that exhibited an extraordinarily high catalase activity was isolated from the drain pool of a plant that uses H(2)O(2) as a bleaching agent. Its cell extract exhibited a catalase activity (19,700 U·mg protein(-1)) that was higher than t...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms13021733
更新日期：2012-01-01 00:00:00
abstract：:Hybrid materials constituted by peptides and synthetic polymers have nowadays a great interest since they can combine the properties and functions of each constitutive block, being also possible to modify the final characteristics by using different topologies. Poly(l-lactide-b-l-phenylalanine) copolymers with various...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms150813247
更新日期：2014-07-29 00:00:00
abstract：:This paper aims at analysing the synthesis of flavonoids, their import and export in plant cell compartments, as well as their involvement in the response to stress, with particular reference to grapevine (Vitis vinifera L.). A multidrug and toxic compound extrusion (MATE) as well as ABC transporters have been demonst...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms140714950
更新日期：2013-07-17 00:00:00
abstract：:Prediction of microRNA-mRNA interaction typically relies on bioinformatic methods, but these methods only suggest the possibility of microRNA binding and may miss important interactions as well as falsely predict others. A major obstacle to the miRNA research has been the lack of experimental procedures for the identi...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms150814753
更新日期：2014-08-22 00:00:00
abstract：:Benzo[a]pyrene (BaP) is a well-known carcinogen formed during the cooking process. Although BaP exposure has been implicated as one of the risk factors for lung cancer in animals and humans, there are only limited data on BaP-induced gastrointestinal cancer. Therefore, this study investigated the protective effects of...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20225533
更新日期：2019-11-06 00:00:00
abstract：:Neuroblastoma (NB) is an aggressive, relapse-prone infancy tumor of the sympathetic nervous system and is the leading cause of death among preschool age diseases, so the search for novel therapeutic targets is crucial. Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development, and in the DNA ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20194764
更新日期：2019-09-25 00:00:00
abstract：:Dual drug-loaded nanotherapeutics can play an important role against the drug resistance and side effects of the single drugs. Doxorubicin and sorafenib were efficiently co-encapsulated by tailor-made poly([R,S]-3-hydroxybutyrate) (PHB) using an emulsion-solvent evaporation method. Subsequent poly(ethylene glycol) (PE...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21197312
更新日期：2020-10-03 00:00:00
abstract：:Pseudomonas aeruginosa and Staphylococcus aureus are two major pathogens involved in a large variety of infections. Their co-occurrence in the same site of infection has been frequently reported and is linked to enhanced virulence and difficulty of treatment. Herein, the antimicrobial and antibiofilm activities of an ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20143604
更新日期：2019-07-23 00:00:00
abstract：:Although platelet-rich fibrin (PRF) has been used in clinical practice for some time, to date, few studies reveal its role as a bioactive scaffold in facilitating meniscal repair. Here, the positive anabolic effects of PRF on meniscocytes harvested from the primary culture of a rabbit meniscus were revealed. The rabbi...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18081722
更新日期：2017-08-07 00:00:00
abstract：:A new approach for encoding DNA sequences as input for DNA sequence analysis is proposed using the error correction coding theory of communication engineering. The encoder was designed as a convolutional code model whose generator matrix is designed based on the degeneracy of codons, with a codon treated in the model ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms14048393
更新日期：2013-04-16 00:00:00
abstract：:Peptide/protein aggregation is implicated in many amyloid diseases. Some amyloidogenic peptides/proteins, such as those implicated in Alzheimer's and Parkinson's diseases, contain multiple amyloidogenic domains connected by "linker" sequences displaying high propensities to form turn structures. Recent studies have de...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms131012169
更新日期：2012-09-25 00:00:00
abstract：:Humans express an expansive and detailed response to wavelength differences within the electromagnetic (EM) spectrum. This is most clearly manifest, and most studied, with respect to a relatively small range of electromagnetic radiation that includes the visible wavelengths with abutting ultraviolet and infrared, and ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21218020
更新日期：2020-10-28 00:00:00
abstract：:Hepatocellular carcinoma (HCC) is a deadly form of liver malignancy with limited treatment options. Amplification and/or overexpression of c-MYC is one of the most frequent genetic events in human HCC. The mammalian target of Rapamycin Complex 1 (mTORC1) is a major functional axis regulating various aspects of cellula...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21228467
更新日期：2020-11-11 00:00:00
abstract：:Over the years, anthropogenic factors have led to cadmium (Cd) accumulation in the environment causing various health problems in humans. Although Cd is not a Fenton-like metal, it induces oxidative stress in various animal models via indirect mechanisms. The degree of Cd-induced oxidative stress depends on the dose, ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms14036116
更新日期：2013-03-18 00:00:00
abstract：:Inflammatory bowel diseases (IBD) are chronic, inflammatory processes that affect the gastrointestinal tract and are mainly represented by ulcerative colitis (UC) and Crohn's disease (CD). Omega 3 (ω3) fatty acids (eicosapentanoic acid and docosahexaenoic acid) show an indispensable role in the inflammatory processes ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,meta分析,评审
doi：10.3390/ijms20194851
更新日期：2019-09-30 00:00:00
abstract：:NAC (NAM, ATAF1/2, and CUC2) transcription factors play important roles in many biological processes, and mainly bind to the NACRS with core sequences "CACG" or "CATGTG" to regulate gene expression. However, whether NAC proteins can bind to other motifs without these core sequences remains unknown. In this study, we e...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19103271
更新日期：2018-10-21 00:00:00
abstract：:The inducible expression of the mitochondrial translocator protein 18 kDa (TSPO) by activated microglia is a prominent, regular feature of acute and chronic-progressive brain pathology. This expression is also the rationale for the continual development of new TSPO binding molecules for the diagnosis of "neuroinflamma...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19092707
更新日期：2018-09-11 00:00:00
abstract：:The gut microbiome plays an important role in obesity and Type 2 diabetes (T2D); however, it remains unclear whether the gut microbiome could clarify the dietary versus genetic origin of these ailments. Moreover, studies examining the gut microbiome in diet- versus genetically induced obesity/T2D in the same experimen...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21103434
更新日期：2020-05-13 00:00:00
abstract：:Animal venoms are small natural mixtures highly enriched in bioactive components. They are known to target at least two important pharmacological classes of cell surface receptors: ion channels and G protein coupled receptors. Since sperm cells express a wide variety of ion channels and membrane receptors, required fo...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21207786
更新日期：2020-10-21 00:00:00
abstract：:Apolipoprotein E (APOE) ε4 gene allele and type 2 diabetes mellitus (T2DM) are prime risk factors for Alzheimer's disease (AD). Despite evidence linking T2DM and apoE4, the mechanism underlying their interaction is yet to be determined. In the present study, we employed a model of APOE-targeted replacement mice and hi...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21041289
更新日期：2020-02-14 00:00:00
abstract：:The presence of CD4 T lymphocytes has been described for several teleost species, while many of the main T cell subsets have not been characterized at a cellular level, because of a lack of suitable tools for their identification, e.g., monoclonal antibodies (mAbs) against cell markers. We previously described the tis...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21114180
更新日期：2020-06-11 00:00:00
abstract：:Polygalacturonase (PG), a large hydrolase family in plants, is involved in pectin disassembly of the cell wall in plants. The present study aims to characterize PG genes and investigate their expression patterns in Solanum lycopersicum. We identified 54 PG genes in the tomato genome and compared their amino acid seque...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19082290
更新日期：2018-08-04 00:00:00
