Human Neuraminidases Have Reduced Activity Towards Modified Sialic Acids on Glycoproteins

2020 ◽  
Author(s):  
Carmanah D. Hunter ◽  
Elizabeth Porter ◽  
Christopher Cairo
Keyword(s):  
Substrate Specificity ◽  
General Trend ◽  
Sialic Acids ◽  
Enzyme Specificity ◽  
Naturally Occurring ◽  
Bovine Submaxillary Mucin ◽  
Reduced Activity

This work investigated the substrate specificity of hNEU enzymes for a glycoprotein substrate (bovine submaxillary mucin) containing 9-<i>O</i>-acetylated and Neu5Gc residues. Using this model substrate, we observe a general trend for hNEU tolerance of Neu5Ac>Neu5Gc>>>Neu5,9Ac<sub>2</sub>, consistent with our previous results with glycolipid substrates. These results expand our understanding of hNEU enzyme specificity and suggest that naturally occurring modifications of sialic acids can play a role in regulating hNEU activity.

Human Neuraminidases Have Reduced Activity Towards Modified Sialic Acids on Glycoproteins

2020 ◽  
Author(s):  
Carmanah D. Hunter ◽  
Elizabeth Porter ◽  
Christopher Cairo
Keyword(s):  
Substrate Specificity ◽  
General Trend ◽  
Sialic Acids ◽  
Enzyme Specificity ◽  
Naturally Occurring ◽  
Bovine Submaxillary Mucin ◽  
Reduced Activity

This work investigated the substrate specificity of hNEU enzymes for a glycoprotein substrate (bovine submaxillary mucin) containing 9-<i>O</i>-acetylated and Neu5Gc residues. Using this model substrate, we observe a general trend for hNEU tolerance of Neu5Ac>Neu5Gc>>>Neu5,9Ac<sub>2</sub>, consistent with our previous results with glycolipid substrates. These results expand our understanding of hNEU enzyme specificity and suggest that naturally occurring modifications of sialic acids can play a role in regulating hNEU activity.

Human Neuraminidases Have Reduced Activity Towards Modified Sialic Acids on Glycoproteins

2020 ◽  
Author(s):  
Carmanah D. Hunter ◽  
Elizabeth Porter ◽  
Christopher Cairo
Keyword(s):  
Substrate Specificity ◽  
General Trend ◽  
Sialic Acids ◽  
Enzyme Specificity ◽  
Naturally Occurring ◽  
Bovine Submaxillary Mucin ◽  
Reduced Activity

This work investigated the substrate specificity of hNEU enzymes for a glycoprotein substrate (bovine submaxillary mucin) containing 9-<i>O</i>-acetylated and Neu5Gc residues. Using this model substrate, we observe a general trend for hNEU tolerance of Neu5Ac>Neu5Gc>>>Neu5,9Ac<sub>2</sub>, consistent with our previous results with glycolipid substrates. These results expand our understanding of hNEU enzyme specificity and suggest that naturally occurring modifications of sialic acids can play a role in regulating hNEU activity.

NMR Assisted Antimicrobial Peptide Designing: Structure Based Modifications and Functional Correlation of a Designed Peptide VG16KRKP

2020 ◽  
Vol 27 (9) ◽  
pp. 1387-1404 ◽  
Author(s):  
Karishma Biswas ◽  
Humaira Ilyas ◽  
Aritreyee Datta ◽  
Anirban Bhunia
Keyword(s):  
Antimicrobial Agents ◽  
Biological Properties ◽  
Structure Characterization ◽  
Drug Resistant ◽  
Functional Correlation ◽  
Naturally Occurring ◽  
High Resolution Nmr ◽  
Different Types ◽  
Reduced Activity ◽  
Poor Stability

Antimicrobial Peptides (AMPs), within their realm incorporate a diverse group of structurally and functionally varied peptides, playing crucial roles in innate immunity. Over the last few decades, the field of AMP has seen a huge upsurge, mainly owing to the generation of the so-called drug resistant ‘superbugs’ as well as limitations associated with the existing antimicrobial agents. Due to their resilient biological properties, AMPs can very well form the sustainable alternative for nextgeneration therapeutic agents. Certain drawbacks associated with existing AMPs are, however, issues of major concern, circumventing which are imperative. These limitations mainly include proteolytic cleavage and hence poor stability inside the biological systems, reduced activity due to inadequate interaction with the microbial membrane, and ineffectiveness because of inappropriate delivery among others. In this context, the application of naturally occurring AMPs as an efficient prototype for generating various synthetic and designed counterparts has evolved as a new avenue in peptide-based therapy. Such designing approaches help to overcome the drawbacks of the parent AMPs while retaining the inherent activity. In this review, we summarize some of the basic NMR structure based approaches and techniques which aid in improving the activity of AMPs, using the example of a 16-residue dengue virus fusion protein derived peptide, VG16KRKP. Using first principle based designing technique and high resolution NMR-based structure characterization we validate different types of modifications of VG16KRKP, highlighting key motifs, which optimize its activity. The approaches and designing techniques presented can support our peers in their drug development work.

scholarly journals Engineering polymerases for applications in synthetic biology

2020 ◽  
Vol 53 ◽  
Author(s):  
Ali Nikoomanzar ◽  
Nicholas Chim ◽  
Eric J. Yik ◽  
John C. Chaput
Keyword(s):  
Cell Division ◽  
Synthetic Biology ◽  
Substrate Specificity ◽  
Physicochemical Properties ◽  
Genetic Information ◽  
Biomedical Applications ◽  
Dna Polymerases ◽  
Enzyme Engineering ◽  
Practical Applications ◽  
Naturally Occurring

Abstract DNA polymerases play a central role in biology by transferring genetic information from one generation to the next during cell division. Harnessing the power of these enzymes in the laboratory has fueled an increase in biomedical applications that involve the synthesis, amplification, and sequencing of DNA. However, the high substrate specificity exhibited by most naturally occurring DNA polymerases often precludes their use in practical applications that require modified substrates. Moving beyond natural genetic polymers requires sophisticated enzyme-engineering technologies that can be used to direct the evolution of engineered polymerases that function with tailor-made activities. Such efforts are expected to uniquely drive emerging applications in synthetic biology by enabling the synthesis, replication, and evolution of synthetic genetic polymers with new physicochemical properties.

Serum concentration of sialic acids in naturally occurring ovine babesiosis

2014 ◽  
Vol 46 (7) ◽  
pp. 1217-1221 ◽  
Author(s):  
Bijan Esmaeilnejad ◽  
Mousa Tavassoli ◽  
Siamak Asri-Rezaei ◽  
Bahram Dalir-Naghadeh ◽  
Seyyed Meysam Abtahi Froushani ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Sialic Acids ◽  
Naturally Occurring

scholarly journals Structural Analysis of Naturally Occurring Sialic Acids

2006 ◽  
pp. 69-92
Author(s):  
Johannis P. Kamerling ◽  
Gerrit J. Gerwig
Keyword(s):  
Structural Analysis ◽  
Sialic Acids ◽  
Naturally Occurring

scholarly journals Substrate-specificity studies on protochlorophyllide reductase in barley (Hordeum vulgare) etioplast membranes

1980 ◽  
Vol 186 (1) ◽  
pp. 267-278 ◽  
Author(s):  
W T Griffiths
Keyword(s):  
Carboxylic Acid ◽  
Methyl Ester ◽  
Hordeum Vulgare ◽  
Substrate Specificity ◽  
Acid Group ◽  
Carboxylic Acid Group ◽  
Naturally Occurring ◽  
Protochlorophyllide Reductase ◽  
Nickel Copper ◽  
Etioplast Membranes

1. The substrate specificity of the enzyme protochlorophyllide reductase in barley (Hordeum vulgare) etioplasts was investigated. 2. It was shown that naturally occurring esterified protochlorophyllide and chemically prepared protochlorophyllide methyl ester are not substrates for the enzyme, suggesting an important role for the C-7 carboxylic acid group in binding of the porphyrin to the enzyme. 3. Removal of magnesium from the protochlorophyllide leads to inactivity of the compound as a substrate for the enzyme. However, activity can be restored by replacing the magnesium with zinc, whereas nickel, copper or cobalt failed to restore substrate activity. 4. Binding of the second substrate, NADPH, to the enzyme probably occurs through the 2'-phosphate group in the coenzyme.

scholarly journals Comprehensive exploration of the translocation, stability and substrate recognition requirements in VIM-2 lactamase

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
John Z Chen ◽  
Douglas M Fowler ◽  
Nobuhiko Tokuriki
Keyword(s):  
Substrate Specificity ◽  
Multidrug Resistant ◽  
Single Amino Acid ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Naturally Occurring ◽  
Amino Acid Variant ◽  
Biochemical Studies ◽  
Different Temperatures ◽  
And Function

Metallo-β-lactamases (MBLs) degrade a broad spectrum of β-lactam antibiotics, and are a major disseminating source for multidrug resistant bacteria. Despite many biochemical studies in diverse MBLs, molecular understanding of the roles of residues in the enzyme’s stability and function, and especially substrate specificity, is lacking. Here, we employ deep mutational scanning (DMS) to generate comprehensive single amino acid variant data on a major clinical MBL, VIM-2, by measuring the effect of thousands of VIM-2 mutants on the degradation of three representative classes of β-lactams (ampicillin, cefotaxime, and meropenem) and at two different temperatures (25°C and 37°C). We revealed residues responsible for expression and translocation, and mutations that increase resistance and/or alter substrate specificity. The distribution of specificity-altering mutations unveiled distinct molecular recognition of the three substrates. Moreover, these function-altering mutations are frequently observed among naturally occurring variants, suggesting that the enzymes have continuously evolved to become more potent resistance genes.

Control of O-glycan synthesis: specificity and inhibition of O-glycan core 1 UDP-galactose:N-acetylgalactosamine-α-R β3-galactosyltransferase from rat liver

1992 ◽  
Vol 70 (2) ◽  
pp. 99-108 ◽  
Author(s):  
Inka Brockhausen ◽  
Gabriele Möller ◽  
Annette Pollex-Krüger ◽  
Volker Rutz ◽  
Hans Paulsen ◽  
...  
Keyword(s):  
Enzyme Inhibition ◽  
Rat Liver ◽  
Enzyme Preparation ◽  
Significant Inhibition ◽  
Control Factor ◽  
Enzyme Specificity ◽  
Acceptor Substrate ◽  
Alternate Pathway ◽  
Derivatives Of ◽  
Reduced Activity

The specificity of glycosyltransferases is a major control factor in the biosynthesis of O-glycans. The enzyme that synthesizes O-glycan core 1, i.e., UDP-galactose:N-acetylgalactosamine-α-R β3-galactosyltransferase (β3-Gal-T; EC 2.4.1.122), was partially purified from rat liver. The enzyme preparation, free of pyrophosphatases, β4-galactosyltransferase, β-galactosidase, and N-acetylglucosaminyltransferase I, was used to study the specificity and inhibition of the β3-Gal-T. β3-Gal-T activity is sensitive to changes in the R-group of the GalNAcα-R acceptor substrate and is stimulated when the R-group is a peptide or an aromatic group. Derivatives of GalNAcα-benzyl were synthesized and tested as potential substrates and inhibitors. Removal or substitution of the 3-hydroxyl or removal of the 4-hydroxyl of GalNAc abolished β3-Gal-T activity. Compounds with modifications of the 3- or 4-hydroxyl of GalNAcα-benzyl did not show significant inhibition. Removal or substitution of the 6-hydroxyl of GalNAc reduced activity slightly and these derivatives acted as competitive substrates. Derivatives with epoxide groups attached to the 6-position of GalNAc acted as substrates and not as inhibitors, with the exception of the photosensitive 6-O-(4,4-azo)pentyl-GalNAcα-benzyl, which inhibited Gal incorporation into GalNAcα-benzyl. The results indicate that the enzyme does not require the 6-hydroxyl of GalNAc, but needs the 3- and the axial 4-hydroxyl as essential requirements for binding and activity. In the usual biochemical O-glycan pathway, core 2 (GlcNAcβ6[Galβ3]GalNAcα-) is formed from core 1 (Galβ3GalNAc-R). We have now demonstrated an alternate pathway that may be of importance in human tissues.Key words: β3-Gal-transferase, mucin synthesis, O-glycan core 1, enzyme specificity, enzyme inhibition.

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