1w1t: Difference between revisions
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[[Image:1w1t.gif|left|200px]]<br /> | [[Image:1w1t.gif|left|200px]]<br /><applet load="1w1t" size="450" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1w1t" size="450" color="white" frame="true" align="right" spinBox="true" | |||
caption="1w1t, resolution 1.90Å" /> | caption="1w1t, resolution 1.90Å" /> | ||
'''CRYSTAL STRUCTURE OF S. MARCESCENS CHITINASE B IN COMPLEX WITH THE CYCLIC DIPEPTIDE INHIBITOR CYCLO-(HIS-L-PRO) AT 1.9 A RESOLUTION'''<br /> | '''CRYSTAL STRUCTURE OF S. MARCESCENS CHITINASE B IN COMPLEX WITH THE CYCLIC DIPEPTIDE INHIBITOR CYCLO-(HIS-L-PRO) AT 1.9 A RESOLUTION'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1W1T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Serratia_marcescens Serratia marcescens] with SO4, CHQ and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] | 1W1T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Serratia_marcescens Serratia marcescens] with SO4, CHQ and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=BC5:Chq Binding Site For Chain B'>BC5</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W1T OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: structure-based inhibitor design]] | [[Category: structure-based inhibitor design]] | ||
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Revision as of 19:16, 18 December 2007
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CRYSTAL STRUCTURE OF S. MARCESCENS CHITINASE B IN COMPLEX WITH THE CYCLIC DIPEPTIDE INHIBITOR CYCLO-(HIS-L-PRO) AT 1.9 A RESOLUTION
OverviewOverview
Family 18 chitinases play an essential role in a range of pathogens and, pests. Several inhibitors are known, including the potent inhibitors, argadin and allosamidin, and the structures of these in complex with, chitinases have been elucidated. Recent structural analysis has revealed, that CI-4 [cyclo-(L-Arg-D-Pro)] inhibits family 18 chitinases by mimicking, the structure of the proposed reaction intermediate. Here we report the, high-resolution structures of four new CI-4 derivatives, cyclo-(L-Arg-L-Pro), cyclo-(Gly-L-Pro), cyclo-(L-His-L-Pro), and, cyclo-(L-Tyr-L-Pro), in complex with a family 18 chitinase. In addition, details of enzyme inhibition and in vivo activity against Saccharomyces, cerevisiae are presented. The structures reveal that the common, cyclo-(Gly-Pro) substructure is sufficient for binding, allowing, modification of the side chain of the nonproline residue. This suggests, that design of cyclic dipeptides with a view to increasing inhibition of, family 18 chitinases should be possible through relatively accessible, chemistry. The derivatives presented here in complex with chitinase B from, Serratia marcescens provide further insight into the mechanism of, inhibition of chitinases by cyclic dipeptides as well as providing a new, scaffold for chitinase inhibitor design.
About this StructureAbout this Structure
1W1T is a Single protein structure of sequence from Serratia marcescens with SO4, CHQ and GOL as ligands. Active as Chitinase, with EC number 3.2.1.14 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structure-based exploration of cyclic dipeptide chitinase inhibitors., Houston DR, Synstad B, Eijsink VG, Stark MJ, Eggleston IM, van Aalten DM, J Med Chem. 2004 Nov 4;47(23):5713-20. PMID:15509170
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