1w9v: Difference between revisions

Revision as of 13:21, 3 May 2008

SPECIFICITY AND AFFINITY OF NATURAL PRODUCT CYCLOPENTAPEPTIDE ARGIFIN AGAINST ASPERGILLUS FUMIGATUS

OverviewOverview

Family 18 chitinases play key roles in organisms ranging from bacteria to man. There is a need for specific, potent inhibitors to probe the function of these chitinases in different organisms. Such molecules could also provide leads for the development of chemotherapeuticals with fungicidal, insecticidal, or anti-inflammatory potential. Recently, two natural product peptides, argifin and argadin, have been characterized, which structurally mimic chitinase-chitooligosaccharide interactions and inhibit a bacterial chitinase in the nM-mM range. Here, we show that these inhibitors also act on human and Aspergillus fumigatus chitinases. The structures of these enzymes in complex with argifin and argadin, together with mutagenesis, fluorescence, and enzymology, reveal that subtle changes in the binding site dramatically affect affinity and selectivity. The data show that it may be possible to develop specific chitinase inhibitors based on the argifin/argadin scaffolds.

About this StructureAbout this Structure

1W9V is a Single protein structure of sequence from Aspergillus fumigatus. Full crystallographic information is available from OCA.

ReferenceReference

Specificity and affinity of natural product cyclopentapeptide inhibitors against A. fumigatus, human, and bacterial chitinases., Rao FV, Houston DR, Boot RG, Aerts JM, Hodkinson M, Adams DJ, Shiomi K, Omura S, van Aalten DM, Chem Biol. 2005 Jan;12(1):65-76. PMID:15664516 Page seeded by OCA on Sat May 3 13:21:27 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1w9v.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1w9v |SIZE=350|CAPTION= <scene name='initialview01'>1w9v</scene>, resolution 2.00&Aring;
+The line below this paragraph, containing "STRUCTURE_1w9v", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=RAG:ARGIFIN'>RAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Chitinase Chitinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.14 3.2.1.14] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1w9v|  PDB=1w9v  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1w9v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w9v OCA], [http://www.ebi.ac.uk/pdbsum/1w9v PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1w9v RCSB]</span>
-}}
 '''SPECIFICITY AND AFFINITY OF NATURAL PRODUCT CYCLOPENTAPEPTIDE ARGIFIN AGAINST ASPERGILLUS FUMIGATUS'''
@@ Line 35: / Line 32: @@
 [[Category: Rao, F V.]]
 [[Category: Shiomi, K.]]
-[[Category: argifin]]
+[[Category: Argifin]]
-[[Category: chitinase]]
+[[Category: Chitinase]]
-[[Category: chitinase inhibitor]]
+[[Category: Chitinase inhibitor]]
-[[Category: cyclopentapeptide inhibitor]]
+[[Category: Cyclopentapeptide inhibitor]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 13:21:27 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:33:15 2008''