1h0i: Difference between revisions

Revision as of 18:15, 2 May 2008

COMPLEX OF A CHITINASE WITH THE NATURAL PRODUCT CYCLOPENTAPEPTIDE ARGIFIN FROM GLIOCLADIU

OverviewOverview

Over the past years, family 18 chitinases have been validated as potential targets for the design of drugs against human pathogens that contain or interact with chitin during their normal life cycles. Thus far, only one potent chitinase inhibitor has been described in detail, the pseudotrisaccharide allosamidin. Recently, however, two potent natural-product cyclopentapeptide chitinase inhibitors, argifin and argadin, were reported. Here, we describe high-resolution crystal structures that reveal the details of the interactions of these cyclopeptides with a family 18 chitinase. The structures are examples of complexes of a carbohydrate-processing enzyme with high-affinity peptide-based inhibitors and show in detail how the peptide backbone and side chains mimic the interactions of the enzyme with chitooligosaccharides. Together with enzymological characterization, the structures explain why argadin shows an order of magnitude stronger inhibition than allosamidin, whereas argifin shows weaker inhibition. The peptides bind to the chitinase in remarkably different ways, which may explain the differences in inhibition constants. The two complexes provide a basis for structure-based design of potent chitinase inhibitors, accessible by standard peptide chemistry.

About this StructureAbout this Structure

1H0I is a Protein complex structure of sequences from Serratia marcescens. Full crystallographic information is available from OCA.

ReferenceReference

High-resolution structures of a chitinase complexed with natural product cyclopentapeptide inhibitors: mimicry of carbohydrate substrate., Houston DR, Shiomi K, Arai N, Omura S, Peter MG, Turberg A, Synstad B, Eijsink VG, van Aalten DM, Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9127-32. Epub 2002 Jul 1. PMID:12093900 Page seeded by OCA on Fri May 2 18:15:29 2008

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OCA

@@ Line 1: / Line 1: @@
 [[Image:1h0i.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1h0i |SIZE=350|CAPTION= <scene name='initialview01'>1h0i</scene>, resolution 2.00&Aring;
+The line below this paragraph, containing "STRUCTURE_1h0i", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+D'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MEA:N-METHYLPHENYLALANINE'>MEA</scene>, <scene name='pdbligand=RGI:METHYLCARBAMIC+ACID'>RGI</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_1h0i|  PDB=1h0i  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h0i OCA], [http://www.ebi.ac.uk/pdbsum/1h0i PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1h0i RCSB]</span>
-}}
 '''COMPLEX OF A CHITINASE WITH THE NATURAL PRODUCT CYCLOPENTAPEPTIDE ARGIFIN FROM GLIOCLADIU'''
@@ Line 35: / Line 32: @@
 [[Category: Synstad, B.]]
 [[Category: Turberg, A.]]
-[[Category: argifin]]
+[[Category: Argifin]]
-[[Category: chitin degradation]]
+[[Category: Chitin degradation]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: inhibitor]]
+[[Category: Inhibitor]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 18:15:29 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:55:11 2008''