1h0i: Difference between revisions

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-[[Image:1h0i.gif|left|200px]]<br />
-<applet load="1h0i" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1h0i, resolution 2.00&Aring;" />
-'''COMPLEX OF A CHITINASE WITH THE NATURAL PRODUCT CYCLOPENTAPEPTIDE ARGIFIN FROM GLIOCLADIU'''<br />
-==Overview==
+==Complex of a chitinase with the natural product cyclopentapeptide argifin from Gliocladium==
-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.
+<StructureSection load='1h0i' size='340' side='right'caption='[[1h0i]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1h0i]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Gliocladium Gliocladium] and [https://en.wikipedia.org/wiki/Serratia_marcescens Serratia marcescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H0I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H0I FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IAS:BETA-L-ASPARTIC+ACID'>IAS</scene>, <scene name='pdbligand=MEA:N-METHYLPHENYLALANINE'>MEA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VR0:N~5~-[N-(METHYLCARBAMOYL)CARBAMIMIDOYL]-L-ORNITHINE'>VR0</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1h0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h0i OCA], [https://pdbe.org/1h0i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h0i RCSB], [https://www.ebi.ac.uk/pdbsum/1h0i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h0i ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CHIB_SERMA CHIB_SERMA]
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h0/1h0i_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1h0i ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-H0I is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Serratia_marcescens Serratia marcescens] with SO4, RGI 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] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H0I OCA].
+*[[Chitinase 3D structures|Chitinase 3D structures]]
+__TOC__
-==Reference==
+</StructureSection>
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12093900 12093900]
+[[Category: Gliocladium]]
-[[Category: Chitinase]]
+[[Category: Large Structures]]
-[[Category: Protein complex]]
 [[Category: Serratia marcescens]]
-[[Category: Aalten, D.M.F.]]
+[[Category: Aalten DMF]]
-[[Category: Arai, N.]]
+[[Category: Arai N]]
-[[Category: Eijsink, V.G.H.]]
+[[Category: Eijsink VGH]]
-[[Category: Houston, D.R.]]
+[[Category: Houston DR]]
-[[Category: Omura, S.]]
+[[Category: Omura S]]
-[[Category: Peter, M.G.]]
+[[Category: Peter MG]]
-[[Category: Shiomi, K.]]
+[[Category: Shiomi K]]
-[[Category: Synstad, B.]]
+[[Category: Synstad B]]
-[[Category: Turberg, A.]]
+[[Category: Turberg A]]
-[[Category: GOL]]
-[[Category: RGI]]
-[[Category: SO4]]
-[[Category: argifin]]
-[[Category: chitin degradation]]
-[[Category: hydrolase]]
-[[Category: inhibitor]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov  5 16:24:46 2007''