Fructose-1,6-bisphosphate aldolase (FBA)–a conserved glycolytic enzyme with virulence functions in bacteria: ‘ill met by moonlight’

2014 ◽  
Vol 42 (6) ◽  
pp. 1792-1795 ◽  
Author(s):  
Fariza Shams ◽  
Neil J. Oldfield ◽  
Karl G. Wooldridge ◽  
David P.J. Turner
Keyword(s):  
Current Knowledge ◽  
Glycolytic Enzyme ◽  
Glycolytic Pathway ◽  
Present Review ◽  
Central Metabolism ◽  
Multifunctional Proteins ◽  
Moonlighting Proteins ◽  
Fructose 1,6 Bisphosphate ◽  
Eukaryotic Organisms ◽  
Moonlighting Functions

Moonlighting proteins constitute an intriguing class of multifunctional proteins. Metabolic enzymes and chaperones, which are often highly conserved proteins in bacteria, archaea and eukaryotic organisms, are among the most commonly recognized examples of moonlighting proteins. Fructose-1,6-bisphosphate aldolase (FBA) is an enzyme involved in the Embden–Meyerhof–Parnas (EMP) glycolytic pathway and in gluconeogenesis. Increasingly, it is also recognized that FBA has additional functions beyond its housekeeping role in central metabolism. In the present review, we summarize the current knowledge of the moonlighting functions of FBA in bacteria.

SAFB1- and SAFB2-mediated transcriptional repression: relevance to cancer

2012 ◽  
Vol 40 (4) ◽  
pp. 826-830 ◽  
Author(s):  
Elaine A. Hong ◽  
Hannah L. Gautrey ◽  
David J. Elliott ◽  
Alison J. Tyson-Capper
Keyword(s):  
Stress Response ◽  
Cell Growth ◽  
Family Member ◽  
Potential Function ◽  
Transcriptional Repression ◽  
Current Knowledge ◽  
Present Review ◽  
Multifunctional Proteins ◽  
Cellular Processes ◽  
Attachment Factor

SAFB1 (scaffold attachment factor B1) and a second family member SAFB2, are multifunctional proteins implicated in a variety of cellular processes including cell growth, apoptosis and stress response. Their potential function as tumour suppressors has been proposed based on well-described roles in tran-scriptional repression. The present review summarizes the current knowledge of SAFB1 and SAFB2 proteins in transcriptional repression with relevance to cancer.

scholarly journals The Expanding Landscape of Moonlighting Proteins in Yeasts

2016 ◽  
Vol 80 (3) ◽  
pp. 765-777 ◽  
Author(s):  
Carlos Gancedo ◽  
Carmen-Lisset Flores ◽  
Juana M. Gancedo
Keyword(s):  
Dna Repair ◽  
Experimental Evidence ◽  
Gene Fusion ◽  
Genetic Manipulation ◽  
Biological Processes ◽  
Multifunctional Proteins ◽  
Moonlighting Proteins ◽  
Moonlighting Functions

SUMMARYMoonlighting proteins are multifunctional proteins that participate in unrelated biological processes and that are not the result of gene fusion. A certain number of these proteins have been characterized in yeasts, and the easy genetic manipulation of these microorganisms has been useful for a thorough analysis of some cases of moonlighting. As the awareness of the moonlighting phenomenon has increased, a growing number of these proteins are being uncovered. In this review, we present a crop of newly identified moonlighting proteins from yeasts and discuss the experimental evidence that qualifies them to be classified as such. The variety of moonlighting functions encompassed by the proteins considered extends from control of transcription to DNA repair or binding to plasminogen. We also discuss several questions pertaining to the moonlighting condition in general. The cases presented show that yeasts are important organisms to be used as tools to understand different aspects of moonlighting proteins.

Structure-Based Virtual Screening and Biochemical Evaluation for the Identification of Novel Trypanosoma brucei Aldolase Inhibitors

2018 ◽  
Vol 18 (5) ◽  
pp. 397-405 ◽  
Author(s):  
Leonardo L.G. Ferreira ◽  
Rafaela S. Ferreira ◽  
David L. Palomino ◽  
Adriano D. Andricopulo
Keyword(s):  
Drug Discovery ◽  
Virtual Screening ◽  
Trypanosoma Brucei ◽  
Enzyme Inhibitor ◽  
Practical Knowledge ◽  
Glycolytic Enzyme ◽  
Structure Based Drug Design ◽  
Biochemical Evaluation ◽  
Dynamics Simulations ◽  
Fructose 1,6 Bisphosphate

Introduction: The glycolytic enzyme fructose-1,6-bisphosphate aldolase is a validated molecular target in human African trypanosomiasis (HAT) drug discovery, a neglected tropical disease (NTD) caused by the protozoan Trypanosoma brucei. Herein, a structure-based virtual screening (SBVS) approach to the identification of novel T. brucei aldolase inhibitors is described. Distinct molecular docking algorithms were used to screen more than 500,000 compounds against the X-ray structure of the enzyme. This SBVS strategy led to the selection of a series of molecules which were evaluated for their activity on recombinant T. brucei aldolase. The effort led to the discovery of structurally new ligands able to inhibit the catalytic activity of the enzyme. Results: The predicted binding conformations were additionally investigated in molecular dynamics simulations, which provided useful insights into the enzyme-inhibitor intermolecular interactions. Conclusion: The molecular modeling results along with the enzyme inhibition data generated practical knowledge to be explored in further structure-based drug design efforts in HAT drug discovery.

scholarly journals Evolutionary Perspectives on the Moonlighting Functions of Bacterial Factors That Support Actin-Based Motility

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Volkan K. Köseoğlu ◽  
Hervé Agaisse
Keyword(s):  
Cell Adhesion ◽  
Host Cell ◽  
Biofilm Formation ◽  
Actin Polymerization ◽  
Current Knowledge ◽  
Bacterial Pathogens ◽  
Actin Nucleation ◽  
Bacterial Aggregation ◽  
Moonlighting Functions ◽  
Evolutionary Perspectives

ABSTRACT Various bacterial pathogens display an intracellular lifestyle and spread from cell to cell through actin-based motility (ABM). ABM requires actin polymerization at the bacterial pole and is mediated by the expression of bacterial factors that hijack the host cell actin nucleation machinery or exhibit intrinsic actin nucleation properties. It is increasingly recognized that bacterial ABM factors, in addition to having a crucial task during the intracellular phase of infection, display “moonlighting” adhesin functions, such as bacterial aggregation, biofilm formation, and host cell adhesion/invasion. Here, we review our current knowledge of ABM factors and their additional functions, and we propose that intracellular ABM functions have evolved from ancestral, extracellular adhesin functions.

scholarly journals Functional cross-talk between allosteric effects of activating and inhibiting ligands underlies PKM2 regulation

2018 ◽  
Author(s):  
Jamie A. Macpherson ◽  
Alina Theisen ◽  
Laura Masino ◽  
Louise Fets ◽  
Paul C. Driscoll ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
High Activity ◽  
Pyruvate Kinase ◽  
Cross Talk ◽  
Glycolytic Enzyme ◽  
Computational Framework ◽  
Allosteric Inhibitor ◽  
Fructose 1,6 Bisphosphate ◽  
Low Activity

ABSTRACTAllosteric regulation is central to the role of the glycolytic enzyme pyruvate kinase M2 (PKM2) in cellular metabolism. Multiple activating and inhibitory allosteric ligands regulate PKM2 activity by controlling the equilibrium between high activity tetramers and low activity dimers and monomers. However, it remains elusive how allosteric inputs upon simultaneous binding of different ligands are integrated to regulate PKM2 activity. Here, we show that, in the presence of the allosteric inhibitor L-phenylalanine (Phe), the activator fructose 1,6-bisphosphate (FBP) can induce PKM2 tetramerisation, but fails to maximally increase enzymatic activity. Guided by a new computational framework we developed to identify residues that mediate FBP-induced allostery, we generated two PKM2 mutants, A327S and C358A, in which activation by FBP remains intact but cannot be attenuated by Phe. Our findings demonstrate a role for residues involved in FBP-induced allostery in enabling the integration of allosteric input from Phe and reveal a mechanism that underlies the co-ordinate regulation of PKM2 activity by multiple allosteric ligands.

scholarly journals Matrix Metalloproteinases: A Review

1993 ◽  
Vol 4 (2) ◽  
pp. 197-250 ◽  
Author(s):  
H. Birkedal-Hansen ◽  
W.G.I. Moore ◽  
M.K. Bodden ◽  
L.J. Windsor ◽  
B. Birkedal-Hansen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Current Knowledge ◽  
Periodontal Diseases ◽  
Present Review ◽  
Transcriptional Level ◽  
Substrate Specificities ◽  
Pathological Conditions ◽  
Final Segment ◽  
Extracellular Level

Matrix metalloproteinases (MMPs) are a family of nine or more highly homologous Zn++endopeptidases that collectively cleave most if not all of the constituents of the extracellular matrix. The present review discusses in detail the primary structures and the overlapping yet distinct substrate specificities of MMPs as well as the mode of activation of the unique MMP precursors. The regulation of MMP activity at the transcriptional level and at the extracellular level (precursor activation, inhibition of activated, mature enzymes) is also discussed. A final segment of the review details the current knowledge of the involvement of MMP in specific developmental or pathological conditions, including human periodontal diseases.

scholarly journals Moonlighting in Mitosis: Analysis of the Mitotic Functions of Transcription and Splicing Factors

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1554 ◽  
Author(s):  
Maria Patrizia Somma ◽  
Evgeniya N. Andreyeva ◽  
Gera A. Pavlova ◽  
Claudia Pellacani ◽  
Elisabetta Bucciarelli ◽  
...  
Keyword(s):  
Evolutionary Process ◽  
Splicing Factors ◽  
Insufficient Data ◽  
Primary Role ◽  
Interphase Nuclei ◽  
Protein Databases ◽  
Moonlighting Proteins ◽  
Bona Fide ◽  
Cellular Compartments ◽  
Moonlighting Functions

Moonlighting proteins can perform one or more additional functions besides their primary role. It has been posited that a protein can acquire a moonlighting function through a gradual evolutionary process, which is favored when the primary and secondary functions are exerted in different cellular compartments. Transcription factors (TFs) and splicing factors (SFs) control processes that occur in interphase nuclei and are strongly reduced during cell division, and are therefore in a favorable situation to evolve moonlighting mitotic functions. However, recently published moonlighting protein databases, which comprise almost 400 proteins, do not include TFs and SFs with secondary mitotic functions. We searched the literature and found several TFs and SFs with bona fide moonlighting mitotic functions, namely they localize to specific mitotic structure(s), interact with proteins enriched in the same structure(s), and are required for proper morphology and functioning of the structure(s). In addition, we describe TFs and SFs that localize to mitotic structures but cannot be classified as moonlighting proteins due to insufficient data on their biochemical interactions and mitotic roles. Nevertheless, we hypothesize that most TFs and SFs with specific mitotic localizations have either minor or redundant moonlighting functions, or are evolving towards the acquisition of these functions.

Triosephosphate metabolism by mature boar spermatozoa

1997 ◽  
Vol 9 (6) ◽  
pp. 577 ◽  
Author(s):  
A. R. Jones
Keyword(s):  
Glycolytic Pathway ◽  
Dihydroxyacetone Phosphate ◽  
Glycolytic Intermediates ◽  
Boar Sperm ◽  
Equilibrium Concentrations ◽  
Fructose 1,6 Bisphosphate ◽  
Boar Spermatozoa

Boar sperm rapidly interconverted dihydroxyacetone phosphate and glyceraldehyde 3-phosphate, produced fructose-1,6-bisphosphate, approximately equilibrium concentrations of fructose 6-phosphate and glucose 6-phosphate but not glycerol or glycerol 3-phosphate. In the presence of 3-chloro-1-hydroxypropanone, an inhibitor of stage 2 of the glycolytic pathway, the triosephosphates were metabolized faster, produced less fructose-1,6-bisphosphate, fructose 6-phosphate and glucose 6-phosphate, but not glycerol or glycerol 3-phosphate. This suggests that these cells may have the capacity to convert glycolytic intermediates into a storage metabolite to conserve carbon atoms for the eventual synthesis of lactate.

WAVE signalling: from biochemistry to biology

2006 ◽  
Vol 34 (1) ◽  
pp. 73-76 ◽  
Author(s):  
S.H. Soderling ◽  
J.D. Scott
Keyword(s):  
Cell Division ◽  
Actin Cytoskeleton ◽  
Rho Gtpase ◽  
Current Knowledge ◽  
Biological Significance ◽  
Molecular Switches ◽  
Small Gtpases ◽  
Present Review ◽  
Cellular Targets ◽  
Syndrome Protein

The small GTPases Rho, Rac and Cdc42 (cell-division cycle 42) function as molecular switches to modulate the actin cytoskeleton. They achieve this by modulating the activity of downstream cellular targets. One group of Rho GTPase effectors, WAVE (Wiskott–Aldrich syndrome protein verprolin homologous)-1, WAVE-2 and WAVE-3, function as scaffolds for actin-based signalling complexes. The present review highlights current knowledge regarding the biochemistry of the WAVE signalling complexes and their biological significance.

scholarly journals Regulation of mRNA cap methylation

2009 ◽  
Vol 425 (2) ◽  
pp. 295-302 ◽  
Author(s):  
Victoria H. Cowling
Keyword(s):  
Gene Expression ◽  
Cell Viability ◽  
Nuclear Export ◽  
Present Review ◽  
Biological Processes ◽  
Experimental Systems ◽  
Efficient Gene ◽  
Cellular Mrnas ◽  
Eukaryotic Organisms ◽  
The Impact

The 7-methylguanosine cap added to the 5′ end of mRNA is essential for efficient gene expression and cell viability. Methylation of the guanosine cap is necessary for the translation of most cellular mRNAs in all eukaryotic organisms in which it has been investigated. In some experimental systems, cap methylation has also been demonstrated to promote transcription, splicing, polyadenylation and nuclear export of mRNA. The present review discusses how the 7-methylguanosine cap is synthesized by cellular enzymes, the impact that the 7-methylguanosine cap has on biological processes, and how the mRNA cap methylation reaction is regulated.

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