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  1. Article ; Online: Structural Motifs at the Telomeres and Their Role in Regulatory Pathways.

    Alanazi, Abeer F R / Parkinson, Gary N / Haider, Shozeb

    Biochemistry

    2024  Volume 63, Issue 7, Page(s) 827–842

    Abstract: Telomeres are specialized structures, found at the ends of linear chromosomes in eukaryotic cells, that play a crucial role in maintaining the stability and integrity of genomes. They are composed of repetitive DNA sequences, ssDNA overhangs, and several ...

    Abstract Telomeres are specialized structures, found at the ends of linear chromosomes in eukaryotic cells, that play a crucial role in maintaining the stability and integrity of genomes. They are composed of repetitive DNA sequences, ssDNA overhangs, and several associated proteins. The length of telomeres is linked to cellular aging in humans, and deficiencies in their maintenance are associated with various diseases. Key structural motifs at the telomeres serve to protect vulnerable chromosomal ends. Telomeric DNA also has the ability to form diverse complex DNA higher-order structures, including T-loops, D-loops, R-loops, G-loops, G-quadruplexes, and i-motifs, in the complementary C-rich strand. While many essential proteins at telomeres have been identified, the intricacies of their interactions and structural details are still not fully understood. This Perspective highlights recent advancements in comprehending the structures associated with human telomeres. It emphasizes the significance of telomeres, explores various telomeric structural motifs, and delves into the structural biology surrounding telomeres and telomerase. Furthermore, telomeric loops, their topologies, and the associated proteins that contribute to the safeguarding of telomeres are discussed.
    MeSH term(s) Humans ; Telomere/genetics ; Telomere/metabolism ; DNA/metabolism ; DNA, Single-Stranded ; G-Quadruplexes ; Telomerase/genetics ; Telomerase/metabolism
    Chemical Substances DNA (9007-49-2) ; DNA, Single-Stranded ; Telomerase (EC 2.7.7.49)
    Language English
    Publishing date 2024-03-14
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1108-3
    ISSN 1520-4995 ; 0006-2960
    ISSN (online) 1520-4995
    ISSN 0006-2960
    DOI 10.1021/acs.biochem.4c00023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Ω-Loop mutations control the dynamics of the active site by modulating a network of hydrogen bonds in PDC-3 β-lactamase.

    Chen, Shuang / Mack, Andrew R / Hujer, Andrea M / Bethel, Christopher R / Bonomo, Robert A / Haider, Shozeb

    bioRxiv : the preprint server for biology

    2024  

    Abstract: The expression of antibiotic-inactivating enzymes, such ... ...

    Abstract The expression of antibiotic-inactivating enzymes, such as
    Language English
    Publishing date 2024-02-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.04.578824
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Dynamical nonequilibrium molecular dynamics reveals the structural basis for allostery and signal propagation in biomolecular systems.

    Oliveira, A Sofia F / Ciccotti, Giovanni / Haider, Shozeb / Mulholland, Adrian J

    The European physical journal. B

    2021  Volume 94, Issue 7, Page(s) 144

    Language English
    Publishing date 2021-07-20
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 1459068-2
    ISSN 1434-6036 ; 1434-6028
    ISSN (online) 1434-6036
    ISSN 1434-6028
    DOI 10.1140/epjb/s10051-021-00157-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Structural Role of N170 in Substrate-Assisted Deacylation in KPC-2 β-Lactamase.

    Parwana, Diksha / Gu, Jing / Chen, Shuang / Bethel, Christopher R / Marshall, Emma / Hujer, Andrea M / Bonomo, Robert A / Haider, Shozeb

    Angewandte Chemie (International ed. in English)

    2024  Volume 63, Issue 12, Page(s) e202317315

    Abstract: The amino acid substitutions in Klebsiella pneumoniae carbapenemase 2 (KPC-2) that have arisen in the clinic are observed to lead to the development of resistance to ceftazidime-avibactam, a preferred treatment for KPC bearing Gram-negative bacteria. ... ...

    Abstract The amino acid substitutions in Klebsiella pneumoniae carbapenemase 2 (KPC-2) that have arisen in the clinic are observed to lead to the development of resistance to ceftazidime-avibactam, a preferred treatment for KPC bearing Gram-negative bacteria. Specific substitutions in the omega loop (R164-D179) result in changes in the structure and function of the enzyme, leading to alterations in substrate specificity, decreased stability, and more recently observed, increased resistance to ceftazidime/avibactam. Using accelerated rare-event sampling well-tempered metadynamics simulations, we explored in detail the structural role of R164 and D179 variants that are described to confer ceftazidime/avibactam resistance. The buried conformation of D179 substitutions produce a pronounced structural disorder in the omega loop - more than R164 mutants, where the crystallographic omega loop structure remains mostly intact. Our findings also reveal that the conformation of N170 plays an underappreciated role impacting drug binding and restricting deacylation. The results further support the hypothesis that KPC-2 D179 variants employ substrate-assisted catalysis for ceftazidime hydrolysis, involving the ring amine of the aminothiazole group to promote deacylation and catalytic turnover. Moreover, the shift in the WT conformation of N170 contributes to reduced deacylation and an altered spectrum of enzymatic activity.
    MeSH term(s) Ceftazidime/chemistry ; Ceftazidime/metabolism ; Anti-Bacterial Agents/chemistry ; beta-Lactamases/metabolism ; Bacterial Proteins/metabolism ; Azabicyclo Compounds ; Amino Acid Substitution ; Microbial Sensitivity Tests ; beta-Lactamase Inhibitors
    Chemical Substances Ceftazidime (9M416Z9QNR) ; beta-lactamase KPC-2 (EC 3.5.2.-) ; Anti-Bacterial Agents ; avibactam (7352665165) ; beta-Lactamases (EC 3.5.2.6) ; Bacterial Proteins ; Azabicyclo Compounds ; beta-Lactamase Inhibitors
    Language English
    Publishing date 2024-02-12
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.202317315
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The blood-to-plasma ratio and predicted GABA

    Manchester, Kieran R / Waters, Laura / Haider, Shozeb / Maskell, Peter D

    Forensic toxicology

    2022  Volume 40, Issue 2, Page(s) 349–356

    Abstract: Purpose: The number of benzodiazepines appearing as new psychoactive substances (NPS) is continually increasing. Information about the pharmacological parameters of these compounds is required to fully understand their potential effects and harms. One ... ...

    Abstract Purpose: The number of benzodiazepines appearing as new psychoactive substances (NPS) is continually increasing. Information about the pharmacological parameters of these compounds is required to fully understand their potential effects and harms. One parameter that has yet to be described is the blood-to-plasma ratio. Knowledge of the pharmacodynamics of designer benzodiazepines is also important, and the use of quantitative structure-activity relationship (QSAR) modelling provides a fast and inexpensive method of predicting binding affinity to the GABA
    Methods: In this work, the blood-to-plasma ratios for six designer benzodiazepines (deschloroetizolam, diclazepam, etizolam, meclonazepam, phenazepam, and pyrazolam) were determined. A previously developed QSAR model was used to predict the binding affinity of nine designer benzodiazepines that have recently appeared.
    Results: Blood-to-plasma values ranged from 0.57 for phenazepam to 1.18 to pyrazolam. Four designer benzodiazepines appearing since 2017 (fluclotizolam, difludiazepam, flualprazolam, and clobromazolam) had predicted binding affinities to the GABA
    Conclusions: This work highlights the diverse nature of the designer benzodiazepines and adds to our understanding of their pharmacology. The greater predicted binding affinities are a potential indication of the increasing potency of designer benzodiazepines appearing on the illicit drugs market.
    MeSH term(s) Receptors, GABA-A ; Benzodiazepines/pharmacology ; Plasma ; Illicit Drugs ; gamma-Aminobutyric Acid
    Chemical Substances Receptors, GABA-A ; Benzodiazepines (12794-10-4) ; Illicit Drugs ; gamma-Aminobutyric Acid (56-12-2)
    Language English
    Publishing date 2022-03-16
    Publishing country Japan
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2274095-8
    ISSN 1860-8965
    ISSN 1860-8965
    DOI 10.1007/s11419-022-00616-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: G-Quadruplexes (GQU).

    Haider, Shozeb / Parkinson, Gary N / Marsh, Thomas C

    Journal of nucleic acids

    2018  Volume 2018, Page(s) 1079191

    Language English
    Publishing date 2018-04-30
    Publishing country United States
    Document type Editorial
    ZDB-ID 2549000-X
    ISSN 2090-021X ; 2090-0201
    ISSN (online) 2090-021X
    ISSN 2090-0201
    DOI 10.1155/2018/1079191
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Control of cell surface expression of GABA

    Yuan, Banghao / Hatchett-Walker, Caroline / Long, Philip / Xu, Zhihan / Stephenson, F Anne / Haider, Shozeb / Jovanovic, Jasmina N

    The Journal of biological chemistry

    2022  Volume 298, Issue 12, Page(s) 102590

    Abstract: Type A γ-aminobutyric acid receptors ( ... ...

    Abstract Type A γ-aminobutyric acid receptors (GABA
    Language English
    Publishing date 2022-10-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2022.102590
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: An Integrated Computational and Experimental Approach to Identifying Inhibitors for SARS-CoV-2 3CL Protease.

    Zhai, Tianhua / Zhang, Fangyuan / Haider, Shozeb / Kraut, Daniel / Huang, Zuyi

    Frontiers in molecular biosciences

    2021  Volume 8, Page(s) 661424

    Abstract: The newly evolved SARS-CoV-2 has caused the COVID-19 pandemic, and the SARS-CoV-2 main protease 3CLpro is essential for the rapid replication of the virus. Inhibiting this protease may open an alternative avenue toward therapeutic intervention. In this ... ...

    Abstract The newly evolved SARS-CoV-2 has caused the COVID-19 pandemic, and the SARS-CoV-2 main protease 3CLpro is essential for the rapid replication of the virus. Inhibiting this protease may open an alternative avenue toward therapeutic intervention. In this work, a computational docking approach was developed to identify potential small-molecule inhibitors for SARS-CoV-2 3CLpro. Totally 288 potential hits were identified from a half-million bioactive chemicals via a protein-ligand docking protocol. To further evaluate the docking results, a quantitative structure activity relationship (QSAR) model of 3CLpro inhibitors was developed based on existing small molecule inhibitors of the 3CLpro
    Language English
    Publishing date 2021-05-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2814330-9
    ISSN 2296-889X
    ISSN 2296-889X
    DOI 10.3389/fmolb.2021.661424
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Future COVID19 surges prediction based on SARS-CoV-2 mutations surveillance.

    Najar, Fares Z / Linde, Evan / Murphy, Chelsea L / Borin, Veniamin A / Wang, Huan / Haider, Shozeb / Agarwal, Pratul K

    eLife

    2023  Volume 12

    Abstract: COVID19 has aptly revealed that airborne viruses such as SARS-CoV-2 with the ability to rapidly mutate combined with high rates of transmission and fatality can cause a deadly worldwide pandemic in a matter of weeks (Plato et al., 2021). Apart from ... ...

    Abstract COVID19 has aptly revealed that airborne viruses such as SARS-CoV-2 with the ability to rapidly mutate combined with high rates of transmission and fatality can cause a deadly worldwide pandemic in a matter of weeks (Plato et al., 2021). Apart from vaccines and post-infection treatment options, strategies for preparedness will be vital in responding to the current and future pandemics. Therefore, there is wide interest in approaches that allow predictions of increase in infections ('surges') before they occur. We describe here real-time genomic surveillance particularly based on mutation analysis, of viral proteins as a methodology for a priori determination of surge in number of infection cases. The full results are available for SARS-CoV-2 at http://pandemics.okstate.edu/covid19/, and are updated daily as new virus sequences become available. This approach is generic and will also be applicable to other pathogens.
    MeSH term(s) Humans ; COVID-19/epidemiology ; Genomics ; Mutation ; SARS-CoV-2/genetics
    Language English
    Publishing date 2023-01-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.82980
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Future COVID19 surges prediction based on SARS-CoV-2 mutations surveillance

    Fares Z Najar / Evan Linde / Chelsea L Murphy / Veniamin A Borin / Huan Wang / Shozeb Haider / Pratul K Agarwal

    eLife, Vol

    2023  Volume 12

    Abstract: COVID19 has aptly revealed that airborne viruses such as SARS-CoV-2 with the ability to rapidly mutate combined with high rates of transmission and fatality can cause a deadly worldwide pandemic in a matter of weeks (Plato et al., 2021). Apart from ... ...

    Abstract COVID19 has aptly revealed that airborne viruses such as SARS-CoV-2 with the ability to rapidly mutate combined with high rates of transmission and fatality can cause a deadly worldwide pandemic in a matter of weeks (Plato et al., 2021). Apart from vaccines and post-infection treatment options, strategies for preparedness will be vital in responding to the current and future pandemics. Therefore, there is wide interest in approaches that allow predictions of increase in infections (‘surges’) before they occur. We describe here real-time genomic surveillance particularly based on mutation analysis, of viral proteins as a methodology for a priori determination of surge in number of infection cases. The full results are available for SARS-CoV-2 at http://pandemics.okstate.edu/covid19/, and are updated daily as new virus sequences become available. This approach is generic and will also be applicable to other pathogens.
    Keywords SARS-CoV-2 ; COVID19 ; coronavirus ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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