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  1. Article ; Online: Exploring NAD

    Jeje, Olamide / Otun, Sarah / Aloke, Chinyere / Achilonu, Ikechukwu

    Biochimie

    2024  Volume 220, Page(s) 84–98

    Abstract: Nicotinamide Adenine Dinucleotide (NAD+), a coenzyme, is ubiquitously distributed and serves crucial functions in diverse biological processes, encompassing redox reactions, energy metabolism, and cellular signalling. This review article explores the ... ...

    Abstract Nicotinamide Adenine Dinucleotide (NAD+), a coenzyme, is ubiquitously distributed and serves crucial functions in diverse biological processes, encompassing redox reactions, energy metabolism, and cellular signalling. This review article explores the intricate realm of NAD + metabolism, with a particular emphasis on the complex relationship between its structure, function, and the pivotal enzyme, Nicotinate Nucleotide Adenylyltransferase (NNAT), also known as nicotinate mononucleotide adenylyltransferase (NaMNAT), in the process of its biosynthesis. Our findings indicate that NAD + biosynthesis in humans and bacteria occurs via the same de novo synthesis route and the pyridine ring salvage pathway. Maintaining NAD homeostasis in bacteria is imperative, as most bacterial species cannot get NAD+ from their surroundings. However, due to lower sequence identity and structurally distant relationship of bacteria, including E. faecium and K. pneumonia, to its human counterpart, inhibiting NNAT, an indispensable enzyme implicated in NAD + biosynthesis, is a viable alternative in curtailing infections orchestrated by E. faecium and K. pneumonia. By merging empirical and computational discoveries and connecting the intricate NAD + metabolism network with NNAT's crucial role, it becomes clear that the synergistic effect of these insights may lead to a more profound understanding of the coenzyme's function and its potential applications in the fields of therapeutics and biotechnology.
    Language English
    Publishing date 2024-01-03
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 120345-9
    ISSN 1638-6183 ; 0300-9084
    ISSN (online) 1638-6183
    ISSN 0300-9084
    DOI 10.1016/j.biochi.2024.01.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Obtaining high yield recombinant Enterococcus faecium nicotinate nucleotide adenylyltransferase for X-ray crystallography and biophysical studies.

    Jeje, Olamide / Pandian, Ramesh / Sayed, Yasien / Achilonu, Ikechukwu

    International journal of biological macromolecules

    2023  Volume 250, Page(s) 126066

    Abstract: Nicotinate nucleotide adenylyltransferase (NNAT) has been a significant research focus on druggable targets, given its indispensability in the biosynthesis of ... ...

    Abstract Nicotinate nucleotide adenylyltransferase (NNAT) has been a significant research focus on druggable targets, given its indispensability in the biosynthesis of NAD
    Language English
    Publishing date 2023-08-05
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 282732-3
    ISSN 1879-0003 ; 0141-8130
    ISSN (online) 1879-0003
    ISSN 0141-8130
    DOI 10.1016/j.ijbiomac.2023.126066
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Obtaining high yield recombinant Enterococcus faecium nicotinate nucleotide adenylyltransferase for X-ray crystallography and biophysical studies

    Jeje, Olamide / Pandian, Ramesh / Sayed, Yasien / Achilonu, Ikechukwu

    International Journal of Biological Macromolecules. 2023 Aug. 05, p.126066-

    2023  , Page(s) 126066–

    Abstract: Nicotinate nucleotide adenylyltransferase (NNAT) has been a significant research focus on druggable targets, given its indispensability in the biosynthesis of NAD⁺, which is crucial to the survival of bacterial pathogens. However, no information is ... ...

    Abstract Nicotinate nucleotide adenylyltransferase (NNAT) has been a significant research focus on druggable targets, given its indispensability in the biosynthesis of NAD⁺, which is crucial to the survival of bacterial pathogens. However, no information is available on the structure-function of Enterococcus faecium NNAT (EfNNAT). This study established the expression and purification protocol for obtaining a high-yield recombinant EfNNAT using the E. coli expression system and a single-step IMAC purification method. Approximately 101 mg of EfNNAT was obtained per 7.8 g of wet E. coli cells, estimated to be over 98 % pure. We further characterized the biophysical structure and determined the three-dimensional structure of the EfNNAT. Biophysical studies revealed a dimeric protein with a higher α-helical composition. The highly stable protein crystalizes in multiple conditions, yielding high-quality crystals diffracting between 1.78 and 2.8 Å. Two high-resolution crystal structures of EfNNAT in its native and adenine-bound forms were determined at 1.90 Å and 1.82 Å, respectively. The X-ray structures of the EfNNAT revealed the presence of phosphate and sulfate ions occupying and interacting with conserved amino acid residues within the putative substrate binding site, hence providing insight into the probable substrate preference of EfNNAT and, consequently, why EfNNAT may not prefer β-nicotinamide mononucleotide as a substrate. With the accessibility to high-resolution structures of EfNNAT, further structural evaluation and drug-based screening can be achieved. Hence, we anticipate that this study will provide the basis for the discovery of structure-based inhibitors against this enzyme.
    Keywords Enterococcus faecium ; Escherichia coli ; X-radiation ; X-ray diffraction ; amino acids ; biosynthesis ; enzymes ; phosphates ; purification methods ; substrate specificity ; sulfates ; Nicotinate nucleotide adenylyltransferase (NNAT) ; Nicotinamide mononucleotide adenylyltransferase (NMNAT) ; Expression ; Purification ; X-ray crystallography
    Language English
    Dates of publication 2023-0805
    Publishing place Elsevier B.V.
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 282732-3
    ISSN 1879-0003 ; 0141-8130
    ISSN (online) 1879-0003
    ISSN 0141-8130
    DOI 10.1016/j.ijbiomac.2023.126066
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Expression, Purification, and Biophysical Characterization of Klebsiella Pneumoniae Nicotinate Nucleotide Adenylyltransferase.

    Daya, Tasvi / Jeje, Olamide / Maake, Reabetswe / Aloke, Chinyere / Khoza, Thandeka / Achilonu, Ikechukwu

    The protein journal

    2022  Volume 41, Issue 1, Page(s) 141–156

    Abstract: Patients in health-care settings develop nosocomial infections due to prolonged hospital stay. The Gram negative Klebsiella pneumoniae (K. pneumoniae), is a bacterial pathogen responsible for most nosocomial infections and are resistant to most current ... ...

    Abstract Patients in health-care settings develop nosocomial infections due to prolonged hospital stay. The Gram negative Klebsiella pneumoniae (K. pneumoniae), is a bacterial pathogen responsible for most nosocomial infections and are resistant to most current antibiotics. Hence, there is need for identification and validation of potential protein targets for design of new generation antibiotics. One of such targets is nicotinate nucleotide adenylyltransferase, an enzyme responsible for redox metabolism. This study focuses on novel expression, purification, and biophysical characterization of NNAT from K. pneumoniae. KpNNAT was over-expressed in T7 express™ Escherichia coli using the pGEX-4 T-1 expressions system and purified to > 98% homogeneity (~ 20 mg KpNNAT/g of the wet cell) using a combination of glutathione-agarose and immobilized Ni
    MeSH term(s) Crystallography, X-Ray ; Escherichia coli/metabolism ; Humans ; Klebsiella pneumoniae/enzymology ; Klebsiella pneumoniae/genetics ; Nicotinamide-Nucleotide Adenylyltransferase/chemistry ; Nicotinamide-Nucleotide Adenylyltransferase/metabolism
    Chemical Substances Nicotinamide-Nucleotide Adenylyltransferase (EC 2.7.7.1) ; nicotinic acid mononucleotide adenylyltransferase (EC 2.7.7.18)
    Language English
    Publishing date 2022-01-27
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2143071-8
    ISSN 1875-8355 ; 1572-3887
    ISSN (online) 1875-8355
    ISSN 1572-3887
    DOI 10.1007/s10930-021-10037-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Combating Lassa Fever in West African Sub-Region: Progress, Challenges, and Future Perspectives.

    Aloke, Chinyere / Obasi, Nwogo Ajuka / Aja, Patrick Maduabuchi / Emelike, Chinedum Uche / Egwu, Chinedu Ogbonnia / Jeje, Olamide / Edeogu, Chuks Oswald / Onisuru, Olalekan Olugbenga / Orji, Obasi Uche / Achilonu, Ikechukwu

    Viruses

    2023  Volume 15, Issue 1

    Abstract: Lassa fever (LF) is a rodent-borne disease that threatens human health in the sub-region of West Africa where the zoonotic host of Lassa virus (LASV) is predominant. Currently, treatment options for LF are limited and since no preventive vaccine is ... ...

    Abstract Lassa fever (LF) is a rodent-borne disease that threatens human health in the sub-region of West Africa where the zoonotic host of Lassa virus (LASV) is predominant. Currently, treatment options for LF are limited and since no preventive vaccine is approved for its infectivity, there is a high mortality rate in endemic areas. This narrative review explores the transmission, pathogenicity of LASV, advances, and challenges of different treatment options. Our findings indicate that genetic diversity among the different strains of LASV and their ability to circumvent the immune system poses a critical challenge to the development of LASV vaccines/therapeutics. Thus, understanding the biochemistry, physiology and genetic polymorphism of LASV, mechanism of evading host immunity are essential for development of effective LASV vaccines/therapeutics to combat this lethal viral disease. The LASV nucleoprotein (NP) is a novel target for therapeutics as it functions significantly in several aspects of the viral life cycle. Consequently, LASV NP inhibitors could be employed as effective therapeutics as they will potentially inhibit LASV replication. Effective preventive control measures, vaccine development, target validation, and repurposing of existing drugs, such as ribavirin, using activity or in silico-based and computational bioinformatics, would aid in the development of novel drugs for LF management.
    MeSH term(s) Humans ; Lassa Fever ; Viral Vaccines ; Lassa virus ; Africa, Western/epidemiology ; Virus Replication
    Chemical Substances Viral Vaccines
    Language English
    Publishing date 2023-01-03
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v15010146
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Effect of Divalent Metal Ion on the Structure, Stability and Function of

    Jeje, Olamide / Maake, Reabetswe / van Deventer, Ruan / Esau, Veruschka / Iwuchukwu, Emmanuel Amarachi / Meyer, Vanessa / Khoza, Thandeka / Achilonu, Ikechukwu

    International journal of molecular sciences

    2021  Volume 23, Issue 1

    Abstract: The continuous threat of drug- ... ...

    Abstract The continuous threat of drug-resistant
    MeSH term(s) Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Binding Sites/physiology ; Cations, Divalent/metabolism ; Computer Simulation ; Crystallography, X-Ray/methods ; Klebsiella pneumoniae/metabolism ; Molecular Docking Simulation/methods ; NAD/metabolism ; Nicotinamide Mononucleotide/analogs & derivatives ; Nicotinamide Mononucleotide/metabolism ; Nicotinamide-Nucleotide Adenylyltransferase/chemistry ; Nicotinamide-Nucleotide Adenylyltransferase/metabolism
    Chemical Substances Bacterial Proteins ; Cations, Divalent ; NAD (0U46U6E8UK) ; Nicotinamide Mononucleotide (1094-61-7) ; nicotinate mononucleotide (321-02-8) ; Nicotinamide-Nucleotide Adenylyltransferase (EC 2.7.7.1) ; nicotinic acid mononucleotide adenylyltransferase (EC 2.7.7.18)
    Language English
    Publishing date 2021-12-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23010116
    Database MEDical Literature Analysis and Retrieval System OnLINE

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