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Structure and inhib...
Structure and inhibition of N-acetylneuraminate lyase from methicillin-resistant Staphylococcus aureus
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North, Rachel A (author)
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Watson, Andrew J. A. (author)
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Pearce, Grant (author)
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Muscroft-Taylor, Andrew C. (author)
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- Friemann, Rosmarie, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,CARe - Centrum för antibiotikaresistensforskning,Department of Chemistry and Molecular Biology,Centre for antibiotic resistance research, CARe
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Fairbanks, Antony J (author)
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Dobson, Renwick C. J. (author)
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(creator_code:org_t)
- 2016-11-07
- 2016
- English.
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In: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 590:23, s. 4414-4428
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Abstract
Subject headings
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- N-Acetylneuraminate lyase is the first committed enzyme in the degradation of sialic acid by bacterial pathogens. In this study, we analyzed the kinetic parameters of N-acetylneuraminate lyase from methicillin-resistant Staphylococcus aureus (MRSA). We determined that the enzyme has a relatively high KM of 3.2 mm, suggesting that flux through the catabolic pathway is likely to be controlled by this enzyme. Our data indicate that sialic acid alditol, a known inhibitor of N-acetylneuraminate lyase enzymes, is a stronger inhibitor of MRSA N-acetylneuraminate lyase than of Clostridium perfringens N-acetylneuraminate lyase. Our analysis of the crystal structure of ligand-free and 2R-sialic acid alditol-bound MRSA N-acetylneuraminate lyase suggests that subtle dynamic differences in solution and/or altered binding interactions within the active site may account for species-specific inhibition.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
Keyword
- Antibiotic resistance
- sialic acid
- structural biology
- X-ray crystallography
Publication and Content Type
- ref (subject category)
- art (subject category)
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