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[[Image:1waw.gif|left|200px]]


{{Structure
==Specificity and affinity of natural product cyclopentapeptide inhibitor Argadin against human chitinase==
|PDB= 1waw |SIZE=350|CAPTION= <scene name='initialview01'>1waw</scene>, resolution 1.75&Aring;
<StructureSection load='1waw' size='340' side='right'caption='[[1waw]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=RIG:ARGADIN'>RIG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> and <scene name='pdbligand=IPA:ISOPROPYL ALCOHOL'>IPA</scene>
<table><tr><td colspan='2'>[[1waw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clonostachys Clonostachys] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WAW FirstGlance]. <br>
|ACTIVITY= [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]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0AR:N-[N-[(4S)-4-AZANYL-5-HYDROXY-5-OXO-PENTYL]CARBAMIMIDOYL]ETHANAMIDE'>0AR</scene>, <scene name='pdbligand=DPR:D-PROLINE'>DPR</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HSE:L-HOMOSERINE'>HSE</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UN1:2-AMINOHEXANEDIOIC+ACID'>UN1</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=1waw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1waw OCA], [https://pdbe.org/1waw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1waw RCSB], [https://www.ebi.ac.uk/pdbsum/1waw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1waw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CHIT1_HUMAN CHIT1_HUMAN] Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity.<ref>PMID:7592832</ref> <ref>PMID:7836450</ref> <ref>PMID:9748235</ref>
== 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/wa/1waw_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=1waw ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


'''SPECIFICITY AND AFFINITY OF NATURAL PRODUCT CYCLOPENTAPEPTIDE INHIBITOR ARGADIN AGAINST HUMAN CHITINASE'''
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<ref>PMID:15664516</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1waw" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Chitinase 3D structures|Chitinase 3D structures]]
 
== References ==
==About this Structure==
<references/>
1WAW is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WAW OCA].
__TOC__
 
</StructureSection>
==Reference==
[[Category: Clonostachys]]
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:[http://www.ncbi.nlm.nih.gov/pubmed/15664516 15664516]
[[Category: Chitinase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Aalten, D M.F Van.]]
[[Category: Adams DJ]]
[[Category: Adams, D J.]]
[[Category: Aerts JMFG]]
[[Category: Aerts, J M.F G.]]
[[Category: Boot RG]]
[[Category: Boot, R G.]]
[[Category: Hodkinson M]]
[[Category: Hodkinson, M.]]
[[Category: Houston DR]]
[[Category: Houston, D R.]]
[[Category: Omura S]]
[[Category: Omura, S.]]
[[Category: Rao FV]]
[[Category: Rao, F V.]]
[[Category: Shiomi K]]
[[Category: Shiomi, K.]]
[[Category: Van Aalten DMF]]
[[Category: GOL]]
[[Category: IPA]]
[[Category: RIG]]
[[Category: SO4]]
[[Category: argadin]]
[[Category: chitinase inhibitor]]
[[Category: cyclopentapeptide inhibitor]]
[[Category: glycosidase]]
[[Category: human chitinase]]
[[Category: hydrolase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:54:33 2008''

Latest revision as of 11:08, 15 November 2023

Specificity and affinity of natural product cyclopentapeptide inhibitor Argadin against human chitinaseSpecificity and affinity of natural product cyclopentapeptide inhibitor Argadin against human chitinase

Structural highlights

1waw is a 2 chain structure with sequence from Clonostachys and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.75Å
Ligands:, , , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CHIT1_HUMAN Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity.[1] [2] [3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Boot RG, Renkema GH, Strijland A, van Zonneveld AJ, Aerts JM. Cloning of a cDNA encoding chitotriosidase, a human chitinase produced by macrophages. J Biol Chem. 1995 Nov 3;270(44):26252-6. PMID:7592832
  2. ↑ Renkema GH, Boot RG, Muijsers AO, Donker-Koopman WE, Aerts JM. Purification and characterization of human chitotriosidase, a novel member of the chitinase family of proteins. J Biol Chem. 1995 Feb 3;270(5):2198-202. PMID:7836450
  3. ↑ Boot RG, Renkema GH, Verhoek M, Strijland A, Bliek J, de Meulemeester TM, Mannens MM, Aerts JM. The human chitotriosidase gene. Nature of inherited enzyme deficiency. J Biol Chem. 1998 Oct 2;273(40):25680-5. PMID:9748235
  4. ↑ Rao FV, Houston DR, Boot RG, Aerts JM, Hodkinson M, Adams DJ, Shiomi K, Omura S, van Aalten DM. Specificity and affinity of natural product cyclopentapeptide inhibitors against A. fumigatus, human, and bacterial chitinases. Chem Biol. 2005 Jan;12(1):65-76. PMID:15664516 doi:http://dx.doi.org/10.1016/j.chembiol.2004.10.013

1waw, resolution 1.75Å

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