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Journal Article

Contribution of amino acids in the Active site of Dipeptidyl Peptidase 4 to the catalytic action of the enzyme

Authors : Gnoth, Kathrin (2023)

Dipeptidyl peptidase 4 (DP4)/CD26 regulates the biological function of various peptide hormones by releasing dipeptides from their N-terminus. The enzyme is a prominent target for the treatment of type-2 diabetes and various DP4 inhibitors have been developed in recent years, but their efficacy and side effects are still an issue. Many available crystal structures of the enzyme give a static picture about enzyme-ligand interactions,&...

Journal article

Protein-protein interfaces as druggable targets: A common motif of the pyridoxal-5’-phosphate-dependent enzymes to receive the coenzyme from its producers

Authors : Aleshin, Vasily A. (2023)

The enzymes using pyridoxal-5’-phosphate (PLP) as the coenzyme encompass more than 300 31 distinct catalytic functions, belonging to five of the seven existing EC classes [1]. Many of these 32 reactions, particularly those involving amino acid metabolism, are critical for not only metabolic 33 switches underlying malformations, but also the elimination of malignant cells. For instance, PLP- 34 dependent transaminases drive T cells activation and...

Journal article

Identification of a new Corin atrial natriuretic peptide-converting enzyme substrate: Agouti-signaling protein (ASIP)

Authors : MacDonald, Bryan T. (2023)

Corin is a transmembrane tethered enzyme best known for processing the hormone atrial natriuretic peptide (ANP) in cardiomyocytes to control electrolyte balance and blood pressure. Loss of function mutations in Corin prevent ANP processing and lead to hypertension. Curiously, Corin loss of function variants also result in lighter coat color pigmentation in multiple species. Corin pigmentation effects are dependent on a functional Agouti locus encoding the ago...

Journal article

The cardiac myosin binding protein-C phosphorylation state as a function of multiple protein kinase and phosphatase activities

Authors : Kampourakis, Thomas (2023)

Phosphorylation of cardiac myosin binding protein-C (cMyBP-C) is a crucial determinant of cardiac myofilament function. Although cMyBP-C phosphorylation by various protein kinases has been extensively studied, the influence of protein phosphatases on cMyBP-C’s multiple phosphorylation sites has remained largely obscure. Here we provide a detailed biochemical characterization of cMyBP-C dephosphorylation by protein phosphatases 1 and 2A (PP1 and PP2A) and deve...

Journal article

Where Initial rates are directly proportional to Substrate concentrations with Application in Molar-mass Determination, Zero-order Specificity constant is Inappropriate

Authors : Udema, Ikechukwu Iloh (2023)

High-ranking scientists" employ the initial rate (vi), expression without consideration for 30 the conditions under which the vi expression can be used. The consequence is the suggestion that the vi 31 is equal to the product of maximum velocity, Vmax, and substrate concentration [S0] divided by the 32 Michaelis-Menten constant, KM. The main objectives are: 1) to show that vi is not equal to Vmax[S0]/KM; 2) to show that&#...

Journal article

Novel exported bifunctional fusion enzymes with chorismate mutase and cyclohexadienyl dehydratase activity: shikimate pathway enzymes teamed up in no man’s land

Authors : Stocker, Christian (2023)

Chorismate mutase (CM) and cyclohexadienyl dehydratase (CDT) catalyze two subsequent reactions in the intracellular biosynthesis of phenylalanine. Surprisingly, exported CMs and CDTs exist in bacterial pathogens. Here, we report the discovery of novel and extremely rare exported bifunctional fusion enzymes, consisting of fused CM and CDT domains. Such enzymes were found in only nine bacterial species belonging to nonpathogenic γ- or β-proteobacteria....

Journal article

Enzymatic assay for UDP-GlcNAc and its application in the parallel assessment of substrate availability and protein O-GlcNAcylation

Authors : Sunden, Marc (2023)

O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous and dynamic yet still relatively poorly understood non-canonical glycosylation of intracellular proteins. Several vital branches of metabolism converge at the hexosamine biosynthetic pathway (HBP) to produce the substrate for protein O-GlcNAcylation the uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). Availability of this metabolite is considered a key regulator of O-GlcNAcylation. Yet UDP-GlcNAc concentrations ...

Journal article

Novel glycoside hydrolase family enzymes from Escherichia coli are associated with osmo-regulated periplasmic glucan synthesis

Authors : motouchi, Sei (2023)

Most Gram-negative bacteria synthesize osmo-regulated periplasmic glucans (OPG) in the periplasm 22 or extracellular space. Many pathogens lose their pathogenicity by knocking out opgG, an OPG23 related gene indispensable for OPG synthesis. However, the biochemical functions of OpgG and OpgD, 24 a paralog of OpgG, have not been elucidated. In this report, structural and functional analyses of OpgG 25 and OpgD from Escherichia coli revealed ...

Journal article

Computationally Guided Design of Novel Angiotensin Converting Enzyme Inhibitors

Authors : Lam, Jennifer D. (2023)

Angiotensin-converting enzyme inhibitors (ACEI) such as Moexipril, Trandolapril, Ramipril, and Perindopril are used to treat hypertension. However, these drugs have undesired side effects. Using computational studies, two new novel drug candidates were designed with improved molecular interactions, ADMET properties, and docking scores compared to Moexipril. Homology analysis was done to determine the best animal model for preclinical studies, and it revealed that Pan troglo...

Journal Article

Dynamic inter-domain transformations mediate the allosteric regulation of human 5, 10-methylenetetrahydrofolate reductase

Authors : Linnea Klara Maryann Blomgren (2023)

One-carbon metabolism drives an extensive network of signalling and biosynthetic pathways 17 essential for cell growth and redox regulation. In all domains of life, 5,10-18 methylenetetrahydrofolate reductase (MTHFR) signals the commitment of folate-derived one-19 carbon units into biosynthesis of the global donor of trans-methylation, S-adenosyl-L-methionine 20 (SAM). Eukaryotic MTHFR appends to its conserved TIM-barrel catalytic domain (CD) a unique 21 regulatory domain (RD)&#...

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