1eyr
From Proteopedia
(New page: 200px<br /><applet load="1eyr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1eyr, resolution 2.20Å" /> '''Structure of a siali...) |
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| - | [[Image:1eyr.gif|left|200px]]<br /><applet load="1eyr" size=" | + | [[Image:1eyr.gif|left|200px]]<br /><applet load="1eyr" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1eyr, resolution 2.20Å" /> | caption="1eyr, resolution 2.20Å" /> | ||
'''Structure of a sialic acid activating synthetase, CMP acylneuraminate synthetase in the presence and absence of CDP'''<br /> | '''Structure of a sialic acid activating synthetase, CMP acylneuraminate synthetase in the presence and absence of CDP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The x-ray crystallographic structure of selenomethionyl | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1EYR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Neisseria_meningitidis Neisseria meningitidis] with CDP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/N-acylneuraminate_cytidylyltransferase N-acylneuraminate cytidylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.43 2.7.7.43] Full crystallographic information is available from [http:// | + | 1EYR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Neisseria_meningitidis Neisseria meningitidis] with <scene name='pdbligand=CDP:'>CDP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/N-acylneuraminate_cytidylyltransferase N-acylneuraminate cytidylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.43 2.7.7.43] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EYR OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Dombrowski, D.]] | [[Category: Dombrowski, D.]] | ||
[[Category: Gilbert, M.]] | [[Category: Gilbert, M.]] | ||
| - | [[Category: Mosimann, S | + | [[Category: Mosimann, S C.]] |
| - | [[Category: Strynadka, N | + | [[Category: Strynadka, N C.]] |
[[Category: Wakarchuk, W.]] | [[Category: Wakarchuk, W.]] | ||
[[Category: CDP]] | [[Category: CDP]] | ||
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[[Category: synthetase]] | [[Category: synthetase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:32:56 2008'' |
Revision as of 10:32, 21 February 2008
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Structure of a sialic acid activating synthetase, CMP acylneuraminate synthetase in the presence and absence of CDP
Overview
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.
About this Structure
1EYR is a Single protein structure of sequence from Neisseria meningitidis with as ligand. Active as N-acylneuraminate cytidylyltransferase, with EC number 2.7.7.43 Full crystallographic information is available from OCA.
Reference
Structure of a sialic acid-activating synthetase, CMP-acylneuraminate synthetase in the presence and absence of CDP., Mosimann SC, Gilbert M, Dombroswki D, To R, Wakarchuk W, Strynadka NC, J Biol Chem. 2001 Mar 16;276(11):8190-6. Epub 2000 Dec 11. PMID:11113120
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