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  1. Article ; Online: Chemical shift assignments of the biotin carboxyl carrier protein domain of L. major Methylcrotonyl-CoA carboxylase.

    Rajak, Manoj Kumar / Sundd, Monica

    Biomolecular NMR assignments

    2021  Volume 15, Issue 2, Page(s) 249–253

    Abstract: Methylcrotonyl-CoA carboxylase (MCCC) is a biotin dependent enzyme, that plays a crucial role in leucine metabolism. The enzyme comprises a biotin carboxylase (BC), a carboxyltransferase (CT), and a biotin carboxyl carrier protein (BCCP) domain. MCCC is ... ...

    Abstract Methylcrotonyl-CoA carboxylase (MCCC) is a biotin dependent enzyme, that plays a crucial role in leucine metabolism. The enzyme comprises a biotin carboxylase (BC), a carboxyltransferase (CT), and a biotin carboxyl carrier protein (BCCP) domain. MCCC is synthesized as an apo-protein, and is posttranslationally modified at a lysine residue, conserved in the biotin carboxyl carrier protein (BCCP) domain. In order to understand the structure, function and interactions of L. major MCCC, we have expressed and characterized its domains. Here we report the complete chemical shift assignments of MCCC BCCP domain of L. major. Furthermore, we have used the assignments to generate a model of the same, using CS-Rosetta. We have also followed its chemical shift perturbations upon biotin modification. Changes were observed at the lysine 51 amide, that undergoes biotin modification, and a few others present in its immediate neighborhood.
    MeSH term(s) Nuclear Magnetic Resonance, Biomolecular
    Language English
    Publishing date 2021-03-22
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2388861-1
    ISSN 1874-270X ; 1874-2718
    ISSN (online) 1874-270X
    ISSN 1874-2718
    DOI 10.1007/s12104-021-10013-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The apo-acyl coenzyme A binding protein of Leishmania major forms a unique 'AXXA' motif mediated dimer.

    Verma, Shalini / Dangi, Rohit Singh / Rajak, Manoj Kumar / Pal, Ravi Kant / Sundd, Monica

    Biochimica et biophysica acta. Proteins and proteomics

    2024  Volume 1872, Issue 4, Page(s) 141016

    Abstract: Acyl-Coenzyme A binding domain containing proteins (ACBDs) are ubiquitous in nearly all eukaryotes. They can exist as a free protein, or a domain of a large, multidomain, multifunctional protein. Besides modularity, ACBDs also display multiplicity. The ... ...

    Abstract Acyl-Coenzyme A binding domain containing proteins (ACBDs) are ubiquitous in nearly all eukaryotes. They can exist as a free protein, or a domain of a large, multidomain, multifunctional protein. Besides modularity, ACBDs also display multiplicity. The same organism may have multiple ACBDs, differing in sequence and organization. By virtue of this diversity, ACBDs perform functions ranging from transport, synthesis, trafficking, signal transduction, transcription, and gene regulation. In plants and some microorganisms, these ACBDs are designated ACBPs (acyl-CoA binding proteins). The simplest ACBD/ACBP is a small, ∼10 kDa, soluble protein, comprising the acyl-CoA binding (ACB) domain. Most of these small ACBDs exist as monomers, while a few show a tendency to oligomerize. In sync with those studies, we report the crystal structure of two ACBDs from Leishmania major, named ACBP
    Language English
    Publishing date 2024-04-12
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2918798-9
    ISSN 1878-1454 ; 1570-9639
    ISSN (online) 1878-1454
    ISSN 1570-9639
    DOI 10.1016/j.bbapap.2024.141016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Impact of COVID-19 first wave on the in-hospital length of stay of operated proximal femur fracture patients in an industrial hospital in Eastern India.

    Kumar, Jayant / Rajak, Manoj Kumar / Chaudhary, Anil Kumar / Thakur, Rajesh

    Journal of family medicine and primary care

    2022  Volume 11, Issue 3, Page(s) 1026–1031

    Abstract: Objective: The objective of this article is to study the impact of coronavirus disease 2019 (COVID-19) pandemic first wave on the in-hospital length of stay of operated proximal femur fractures.: Materials and methods: A retrospective analysis of ... ...

    Abstract Objective: The objective of this article is to study the impact of coronavirus disease 2019 (COVID-19) pandemic first wave on the in-hospital length of stay of operated proximal femur fractures.
    Materials and methods: A retrospective analysis of data collected through the electronic record system of the hospital, after applying inclusion and exclusion criteria, was done. The data were collected from the pre-pandemic, early part first wave and later part first wave of COVID-19 pandemic to calculate the average preoperative stay (POS) and total length of stay (LOS) of operated proximal femur fracture patients. Also, a sub-analysis of POS and LOS was done as per age (male/female), sex (<60/≥60 years) and fracture subtype (intertrochanteric, neck of femur and subtrochanteric fracture) of the patients to study if any of these had a significant direct impact on the POS and LOS.
    Results: The LOS and POS were found to be significantly increased during early part of first wave of COVID-19 pandemic in comparison to the pre-pandemic era (13.6 ± 7.7 days vs. 11.1 ± 5.7 days). The later part of the first wave of the pandemic however saw the LOS and POS to return to near pre-pandemic values, although still remaining higher.
    Conclusion: The study highlights that unpreparedness during the early part of the unprecedented pandemic event leads to a significant increase in LOS of operated patients with its associated implications; however, prompt action by the government, hospital administration and hospital staff the LOS could be reduced to near pre-pandemic values in the later part of the first wave of the pandemic. Analysis of the causes that lead to a significant increase in LOS can help for better future management of similar events in future.
    Language English
    Publishing date 2022-03-10
    Publishing country India
    Document type Journal Article
    ZDB-ID 2735275-4
    ISSN 2278-7135 ; 2249-4863
    ISSN (online) 2278-7135
    ISSN 2249-4863
    DOI 10.4103/jfmpc.jfmpc_1486_21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Estimation of the wind energy potential for coastal locations in India using the Weibull model

    Deep, Sneh / Sarkar, Arnab / Ghawat, Mayur / Rajak, Manoj Kumar

    Renewable energy. 2020 Dec., v. 161

    2020  

    Abstract: Wind energy has exhibited the fastest growth of all renewable energy sources. Available wind energy potential for use by wind turbines has been found to be highly overestimated by existing methodologies when the wind energy potential is assessed from the ...

    Abstract Wind energy has exhibited the fastest growth of all renewable energy sources. Available wind energy potential for use by wind turbines has been found to be highly overestimated by existing methodologies when the wind energy potential is assessed from the total wind speed data because the wind turbine operates between cut-in and cut-out wind speeds. While applying existing methodologies, wind power density is overestimated on average by nearly 25% compared to the actual wind power available to a wind turbine. Hence, for estimating wind energy potential, availability factors and wind energy between cut-in and rated wind speeds should be properly estimated using Weibull models. The appropriateness of different methods of estimating Weibull parameters are site specific. In this article, a novel method has been developed for estimating the actual wind power available to the wind turbine. The parent two-parameter Weibull model can be used to determine the availability factor, whereas when determining the available wind energy between the cut-in and rated wind speeds, wind speed data should be refitted in the range defined by the cut-in and rated wind speeds using a three-parameter Weibull model, where the location parameter can be equated to the cut-in wind speed.
    Keywords Weibull statistics ; wind power ; wind speed ; wind turbines ; India
    Language English
    Dates of publication 2020-12
    Size p. 319-339.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 2001449-1
    ISSN 0960-1481
    ISSN 0960-1481
    DOI 10.1016/j.renene.2020.07.054
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Leishmania major biotin protein ligase forms a unique cross-handshake dimer.

    Rajak, Manoj Kumar / Bhatnagar, Sonika / Pandey, Shubhant / Kumar, Sunil / Verma, Shalini / Patel, Ashok Kumar / Sundd, Monica

    Acta crystallographica. Section D, Structural biology

    2021  Volume 77, Issue Pt 4, Page(s) 510–521

    Abstract: Biotin protein ligase catalyses the post-translational modification of biotin carboxyl carrier protein (BCCP) domains, a modification that is crucial for the function of several carboxylases. It is a two-step process that results in the covalent ... ...

    Abstract Biotin protein ligase catalyses the post-translational modification of biotin carboxyl carrier protein (BCCP) domains, a modification that is crucial for the function of several carboxylases. It is a two-step process that results in the covalent attachment of biotin to the ϵ-amino group of a conserved lysine of the BCCP domain of a carboxylase in an ATP-dependent manner. In Leishmania, three mitochondrial enzymes, acetyl-CoA carboxylase, methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase, depend on biotinylation for activity. In view of the indispensable role of the biotinylating enzyme in the activation of these carboxylases, crystal structures of L. major biotin protein ligase complexed with biotin and with biotinyl-5'-AMP have been solved. L. major biotin protein ligase crystallizes as a unique dimer formed by cross-handshake interactions of the hinge region of the two monomers formed by partial unfolding of the C-terminal domain. Interestingly, the substrate (BCCP domain)-binding site of each monomer is occupied by its own C-terminal domain in the dimer structure. This was observed in all of the crystals that were obtained, suggesting a closed/inactive conformation of the enzyme. Size-exclusion chromatography studies carried out using high protein concentrations (0.5 mM) suggest the formation of a concentration-dependent dimer that exists in equilibrium with the monomer.
    MeSH term(s) Binding Sites ; Biotinylation ; Carbon-Nitrogen Ligases/chemistry ; Carrier Proteins/chemistry ; Dimerization ; Leishmania major/enzymology ; Leishmaniasis, Cutaneous/microbiology ; Protein Conformation ; Protein Domains ; Protozoan Proteins/chemistry
    Chemical Substances Carrier Proteins ; Protozoan Proteins ; Carbon-Nitrogen Ligases (EC 6.3.-)
    Language English
    Publishing date 2021-03-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2968623-4
    ISSN 2059-7983 ; 0907-4449
    ISSN (online) 2059-7983
    ISSN 0907-4449
    DOI 10.1107/S2059798321001418
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Drug repurposing screen identifies lonafarnib as respiratory syncytial virus fusion protein inhibitor.

    Sake, Svenja M / Zhang, Xiaoyu / Rajak, Manoj Kumar / Urbanek-Quaing, Melanie / Carpentier, Arnaud / Gunesch, Antonia P / Grethe, Christina / Matthaei, Alina / Rückert, Jessica / Galloux, Marie / Larcher, Thibaut / Le Goffic, Ronan / Hontonnou, Fortune / Chatterjee, Arnab K / Johnson, Kristen / Morwood, Kaycie / Rox, Katharina / Elgaher, Walid A M / Huang, Jiabin /
    Wetzke, Martin / Hansen, Gesine / Fischer, Nicole / Eléouët, Jean-Francois / Rameix-Welti, Marie-Anne / Hirsch, Anna K H / Herold, Elisabeth / Empting, Martin / Lauber, Chris / Schulz, Thomas F / Krey, Thomas / Haid, Sibylle / Pietschmann, Thomas

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 1173

    Abstract: Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infection in infants, older adults and the immunocompromised. Effective directly acting antivirals are not yet available for clinical use. To address this, we screen the ...

    Abstract Respiratory syncytial virus (RSV) is a common cause of acute lower respiratory tract infection in infants, older adults and the immunocompromised. Effective directly acting antivirals are not yet available for clinical use. To address this, we screen the ReFRAME drug-repurposing library consisting of 12,000 small molecules against RSV. We identify 21 primary candidates including RSV F and N protein inhibitors, five HSP90 and four IMPDH inhibitors. We select lonafarnib, a licensed farnesyltransferase inhibitor, and phase III candidate for hepatitis delta virus (HDV) therapy, for further follow-up. Dose-response analyses and plaque assays confirm the antiviral activity (IC
    MeSH term(s) Animals ; Female ; Mice ; Dibenzocycloheptenes ; Drug Repositioning ; Piperidines/pharmacology ; Piperidines/therapeutic use ; Pyridines ; Respiratory Syncytial Virus Infections/drug therapy ; Viral Fusion Proteins/genetics ; Viral Fusion Proteins/chemistry
    Chemical Substances Dibenzocycloheptenes ; lonafarnib (IOW153004F) ; Piperidines ; Pyridines ; Viral Fusion Proteins
    Language English
    Publishing date 2024-02-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45241-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Bipolar hemiarthroplasty for intracapsular femoral neck fractures in elderly patients.

    Rajak, Manoj Kumar / Jha, Ramkinkar / Kumar, Pankaj / Thakur, Rajesh

    Journal of orthopaedic surgery (Hong Kong)

    2013  Volume 21, Issue 3, Page(s) 313–316

    Abstract: Purpose: To report outcome of 30 patients who underwent bipolar hemiarthroplasty for intracapsular femoral neck fractures.: Methods: 18 women and 12 men aged 56 to 86 (mean, 70) years with Garden type III (n=7) or IV (n=23) intracapsular femoral neck ...

    Abstract Purpose: To report outcome of 30 patients who underwent bipolar hemiarthroplasty for intracapsular femoral neck fractures.
    Methods: 18 women and 12 men aged 56 to 86 (mean, 70) years with Garden type III (n=7) or IV (n=23) intracapsular femoral neck fractures underwent cemented (n=5) or uncemented (n=25) bipolar hemiarthroplasty. Pain was evaluated using the visual analogue score. Mobility status was classified as ambulation with or without aid (a cane or walker). Stability of the prosthesis was classified as stable or unstable. Functional outcome was evaluated using the Harris Hip Score.
    Results: The mean length of hospital stay was 15.3 (range, 4-29) days. At the 6-month follow-up, 21 patients had no pain, 6 had mild pain, and 3 had moderate pain. The mean Harris Hip Score was 83.1; functional outcome was excellent in 10 patients, good in 13, fair in 5, and poor in 2. The latter 2 were non-ambulatory; one of whom had sustained a periprosthetic fracture intra-operatively, which was managed by encerclage wiring, and the other had a neglected prosthetic dislocation at 3 months, which was converted to an excision arthroplasty.
    Conclusion: Bipolar hemiarthroplasty conferred good short-term outcome.
    MeSH term(s) Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip/methods ; Female ; Femoral Neck Fractures/physiopathology ; Femoral Neck Fractures/surgery ; Follow-Up Studies ; Fracture Healing ; Hemiarthroplasty/methods ; Hip Joint/physiopathology ; Hip Joint/surgery ; Hip Prosthesis ; Humans ; Male ; Middle Aged ; Range of Motion, Articular/physiology ; Recovery of Function ; Retrospective Studies ; Time Factors ; Treatment Outcome
    Language English
    Publishing date 2013-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 1493368-8
    ISSN 2309-4990 ; 1022-5536
    ISSN (online) 2309-4990
    ISSN 1022-5536
    DOI 10.1177/230949901302100310
    Database MEDical Literature Analysis and Retrieval System OnLINE

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