1f9g
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| , resolution 2.00Å | |||||||
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| Ligands: | |||||||
| Activity: | Hyaluronate lyase, with EC number 4.2.2.1 | ||||||
| Related: | 1egu, 1f1s
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF STREPTOCOCCUS PNEUMONIAE HYALURONATE LYASE COCRYSTALLIZED WITH ASCORBIC ACID
OverviewOverview
Enzyme activity measurement showed that L-ascorbic acid (vitamin C (Vc)) competitively inhibits the hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase. The complex crystal structure of this enzyme with Vc was determined at 2.0 A resolution. One Vc molecule was found to bind to the active site of the enzyme. The Vc carboxyl group provides the negative charges that lead the molecule into the highly positively charged cleft of the enzyme. The Vc ring system forms hydrophobic interactions with the side chain of Trp-292, which is one of the aromatic patch residues of this enzyme responsible for the selection of the cleavage sites on the substrate chain. The binding of Vc inhibits the substrate binding at hyaluronan 1, 2, and 3 (HA1, HA2, and HA3) catalytic positions. The high concentration of Vc in human tissues probably provides a low level of natural resistance to the pneumococcal invasion. This is the first time that Vc the direct inhibition on the bacterial "spreading factor" was reported, and Vc is also the first chemical that has been shown experimentally to have an inhibitory effect on bacterial hyaluronate lyase. These studies also highlight the possible structural requirement for the design of a stronger inhibitor of bacterial hyaluronate lyase.
About this StructureAbout this Structure
1F9G is a Single protein structure of sequence from Streptococcus pneumoniae. Full crystallographic information is available from OCA.
ReferenceReference
Vitamin C inhibits the enzymatic activity of Streptococcus pneumoniae hyaluronate lyase., Li S, Taylor KB, Kelly SJ, Jedrzejas MJ, J Biol Chem. 2001 May 4;276(18):15125-30. Epub 2001 Jan 12. PMID:11278838
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