1F9G

CRYSTAL STRUCTURE OF STREPTOCOCCUS PNEUMONIAE HYALURONATE LYASE COCRYSTALLIZED WITH ASCORBIC ACID

Summary for 1F9G

• Entry DOI: 10.2210/pdb1f9g/pdb
• Related: 1egu 1f1s
• Descriptor: HYALURONATE LYASE, ASCORBIC ACID (3 entities in total)
• Functional Keywords: ascorbic acid binds to the indole group of trp292, transmembrane, lyase
• Biological source: Streptococcus pneumoniae
• Cellular location: Secreted, cell wall; Peptidoglycan-anchor (Potential): Q54873
• Total number of polymer chains: 1
• Total formula weight: 83738.06

Authors

Li, S.,Jedrzejas, M.J. (deposition date: 2000-07-10, release date: 2001-05-16, Last modification date: 2024-05-22)

Primary citation

Li, S.,Taylor, K.B.,Kelly, S.J.,Jedrzejas, M.J.
Vitamin C inhibits the enzymatic activity of Streptococcus pneumoniae hyaluronate lyase.
J.Biol.Chem., 276:15125-15130, 2001

PubMed Abstract: 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.

PubMed: 11278838
DOI: 10.1074/jbc.M011102200

Experimental method

X-RAY DIFFRACTION (2 Å)