1EZI

Structure of a sialic acid activating synthetase, CMP acylneuraminate synthetase in the presence and absence of CDP

Summary for 1EZI

• Entry DOI: 10.2210/pdb1ezi/pdb
• Related: 1EYR
• Descriptor: CMP-N-ACETYLNEURAMINIC ACID SYNTHETASE (2 entities in total)
• Functional Keywords: homodimer, alpha-beta-alpha, transferase
• Biological source: Neisseria meningitidis
• Cellular location: Cytoplasm: P0A0Z8
• Total number of polymer chains: 2
• Total formula weight: 50309.77

Authors

Mosimann, S.C.,Gilbert, M.,Dombrowski, D.,Wakarchuk, W.,Strynadka, N.C. (deposition date: 2000-05-11, release date: 2001-02-14, Last modification date: 2024-10-30)

Primary citation

Mosimann, S.C.,Gilbert, M.,Dombroswki, D.,To, R.,Wakarchuk, W.,Strynadka, N.C.
Structure of a sialic acid-activating synthetase, CMP-acylneuraminate synthetase in the presence and absence of CDP.
J.Biol.Chem., 276:8190-8196, 2001

PubMed Abstract: The x-ray crystallographic structure of selenomethionyl cytosine-5'-monophosphate-acylneuraminate synthetase (CMP-NeuAc synthetase) from Neisseria meningitidis has been determined at 2.0-A resolution using multiple-wavelength anomalous dispersion phasing, and a second structure, in the presence of the substrate analogue CDP, has been determined at 2.2-A resolution by molecular replacement. This work identifies the active site residues for this class of enzyme for the first time. The detailed interactions between the enzyme and CDP within the mononucleotide-binding pocket are directly observed, and the acylneuraminate-binding pocket has also been identified. A model of acylneuraminate bound to CMP-NeuAc synthetase has been constructed and provides a structural basis for understanding the mechanism of production of "activated" sialic acids. Sialic acids are key saccharide components on the surface of mammalian cells and can be virulence factors in a variety of bacterial species (e.g. Neisseria, Haemophilus, group B streptococci, etc.). As such, the identification of the bacterial CMP-NeuAc synthetase active site can serve as a starting point for rational drug design strategies.

PubMed: 11113120
DOI: 10.1074/jbc.M007235200

Experimental method

X-RAY DIFFRACTION (2 Å)