1w3y
From Proteopedia
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| - | [[Image:1w3y.gif|left|200px]] | + | [[Image:1w3y.gif|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF S. PNEUMONIAE HYALURONATE LYASE IN COMPLEX WITH PALMITOYL-VITAMIN C''' | + | {{Structure |
| + | |PDB= 1w3y |SIZE=350|CAPTION= <scene name='initialview01'>1w3y</scene>, resolution 1.65Å | ||
| + | |SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene> | ||
| + | |LIGAND= <scene name='pdbligand=XYL:D-XYLITOL'>XYL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=PVC:(2E,4R,5S)-2,3,4,5-TETRAHYDROXY-6-(PALMITOYLOXY)HEX-2-ENOIC ACID'>PVC</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Hyaluronate_lyase Hyaluronate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.2.1 4.2.2.1] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF S. PNEUMONIAE HYALURONATE LYASE IN COMPLEX WITH PALMITOYL-VITAMIN C''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1W3Y is a [ | + | 1W3Y is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W3Y OCA]. |
==Reference== | ==Reference== | ||
| - | L-Ascorbic acid 6-hexadecanoate, a potent hyaluronidase inhibitor. X-ray structure and molecular modeling of enzyme-inhibitor complexes., Botzki A, Rigden DJ, Braun S, Nukui M, Salmen S, Hoechstetter J, Bernhardt G, Dove S, Jedrzejas MJ, Buschauer A, J Biol Chem. 2004 Oct 29;279(44):45990-7. Epub 2004 Aug 18. PMID:[http:// | + | L-Ascorbic acid 6-hexadecanoate, a potent hyaluronidase inhibitor. X-ray structure and molecular modeling of enzyme-inhibitor complexes., Botzki A, Rigden DJ, Braun S, Nukui M, Salmen S, Hoechstetter J, Bernhardt G, Dove S, Jedrzejas MJ, Buschauer A, J Biol Chem. 2004 Oct 29;279(44):45990-7. Epub 2004 Aug 18. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15322107 15322107] |
[[Category: Hyaluronate lyase]] | [[Category: Hyaluronate lyase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: peptidoglycan-anchor]] | [[Category: peptidoglycan-anchor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:51:46 2008'' |
Revision as of 12:51, 20 March 2008
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| , resolution 1.65Å | |||||||
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| Sites: | |||||||
| Ligands: | , and | ||||||
| Activity: | Hyaluronate lyase, with EC number 4.2.2.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF S. PNEUMONIAE HYALURONATE LYASE IN COMPLEX WITH PALMITOYL-VITAMIN C
Overview
Hyaluronidases are enzymes that degrade hyaluronan, an important component of the extracellular matrix. The mammalian hyaluronidases are considered to be involved in many (patho)physiological processes like fertilization, tumor growth, and metastasis. Bacterial hyaluronidases, also termed hyaluronate lyases, contribute to the spreading of microorganisms in tissues. Such roles for hyaluronidases suggest that inhibitors could be useful pharmacological tools. Potent and selective inhibitors are not known to date, although L-ascorbic acid has been reported to be a weak inhibitor of Streptococcus pneumoniae hyaluronate lyase (SpnHL). The x-ray structure of SpnHL complexed with L-ascorbic acid has been elucidated suggesting that additional hydrophobic interactions might increase inhibitory activity. Here we show that L-ascorbic acid 6-hexadecanoate (Vcpal) is a potent inhibitor of both streptococcal and bovine testicular hyaluronidase (BTH). Vcpal showed strong inhibition of Streptococcus agalactiae hyaluronate lyase with an IC(50) of 4 microM and weaker inhibition of SpnHL and BTH with IC(50) values of 100 and 56 microM, respectively. To date, Vcpal has proved to be one of the most potent inhibitors of hyaluronidase. We also determined the x-ray structure of the SpnHL-Vcpal complex and confirmed the hypothesis that additional hydrophobic interactions with Phe-343, His-399, and Thr-400 in the active site led to increased inhibition. A homology structural model of BTH was also generated to suggest binding modes of Vcpal to this hyaluronidase. The long alkyl chain seemed to interact with an extended, hydrophobic channel formed by mostly conserved amino acids Ala-84, Leu-91, Tyr-93, Tyr-220, and Leu-344 in BTH.
About this Structure
1W3Y is a Single protein structure of sequence from Streptococcus pneumoniae. Full crystallographic information is available from OCA.
Reference
L-Ascorbic acid 6-hexadecanoate, a potent hyaluronidase inhibitor. X-ray structure and molecular modeling of enzyme-inhibitor complexes., Botzki A, Rigden DJ, Braun S, Nukui M, Salmen S, Hoechstetter J, Bernhardt G, Dove S, Jedrzejas MJ, Buschauer A, J Biol Chem. 2004 Oct 29;279(44):45990-7. Epub 2004 Aug 18. PMID:15322107
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