3rm9

From Proteopedia

(Difference between revisions)

Revision as of 10:16, 22 June 2022

AMCase in complex with Compound 3

Structural highlights

3rm9 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3rm4, 3rm8, 3rme
Gene:	CHIA (HUMAN)
Activity:	Chitinase, with EC number 3.2.1.14
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CHIA_HUMAN] Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to IL-13 and inflammation in response to IL-13. Stimulates chemokine production by pulmonary epithelial cells. Protects lung epithelial cells against apoptosis and promotes phosphorylation of AKT1. Its function in the inflammatory response and in protecting cells against apoptosis is inhibited by allosamidin, suggesting that the function of this protein depends on carbohydrate binding.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Acidic mammalian chitinase (AMCase) is a member of the glycosyl hydrolase 18 family (EC 3.2.1.14) that has been implicated in the pathophysiology of allergic airway disease such as asthma. Small molecule inhibitors of AMCase were identified using a combination of high-throughput screening, fragment screening, and virtual screening techniques and characterized by enzyme inhibition and NMR and Biacore binding experiments. X-ray structures of the inhibitors in complex with AMCase revealed that the larger more potent HTS hits, e.g. 5-(4-(2-(4-bromophenoxy)ethyl)piperazine-1-yl)-1H-1,2,4-triazol-3-amine 1, spanned from the active site pocket to a hydrophobic pocket. Smaller fragments identified by FBS occupy both these pockets independently and suggest potential strategies for linking fragments. Compound 1 is a 200 nM AMCase inhibitor which reduced AMCase enzymatic activity in the bronchoalveolar lavage fluid in allergen-challenged mice after oral dosing.

Identification and characterization of acidic mammalian chitinase inhibitors.,Cole DC, Olland AM, Jacob J, Brooks J, Bursavich MG, Czerwinski R, DeClercq C, Johnson M, Joseph-McCarthy D, Ellingboe JW, Lin L, Nowak P, Presman E, Strand J, Tam A, Williams CM, Yao S, Tsao DH, Fitz LJ J Med Chem. 2010 Aug 26;53(16):6122-8. PMID:20666458^[5]

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

References

↑ Boot RG, Blommaart EF, Swart E, Ghauharali-van der Vlugt K, Bijl N, Moe C, Place A, Aerts JM. Identification of a novel acidic mammalian chitinase distinct from chitotriosidase. J Biol Chem. 2001 Mar 2;276(9):6770-8. Epub 2000 Nov 20. PMID:11085997 doi:http://dx.doi.org/10.1074/jbc.M009886200
↑ Hartl D, He CH, Koller B, Da Silva CA, Homer R, Lee CG, Elias JA. Acidic mammalian chitinase is secreted via an ADAM17/epidermal growth factor receptor-dependent pathway and stimulates chemokine production by pulmonary epithelial cells. J Biol Chem. 2008 Nov 28;283(48):33472-82. doi: 10.1074/jbc.M805574200. Epub 2008, Sep 29. PMID:18824549 doi:http://dx.doi.org/10.1074/jbc.M805574200
↑ Hartl D, He CH, Koller B, Da Silva CA, Kobayashi Y, Lee CG, Flavell RA, Elias JA. Acidic mammalian chitinase regulates epithelial cell apoptosis via a chitinolytic-independent mechanism. J Immunol. 2009 Apr 15;182(8):5098-106. doi: 10.4049/jimmunol.0803446. PMID:19342690 doi:http://dx.doi.org/10.4049/jimmunol.0803446
↑ Seibold MA, Reese TA, Choudhry S, Salam MT, Beckman K, Eng C, Atakilit A, Meade K, Lenoir M, Watson HG, Thyne S, Kumar R, Weiss KB, Grammer LC, Avila P, Schleimer RP, Fahy JV, Rodriguez-Santana J, Rodriguez-Cintron W, Boot RG, Sheppard D, Gilliland FD, Locksley RM, Burchard EG. Differential enzymatic activity of common haplotypic versions of the human acidic Mammalian chitinase protein. J Biol Chem. 2009 Jul 17;284(29):19650-8. doi: 10.1074/jbc.M109.012443. Epub 2009, May 12. PMID:19435888 doi:http://dx.doi.org/10.1074/jbc.M109.012443
↑ Cole DC, Olland AM, Jacob J, Brooks J, Bursavich MG, Czerwinski R, DeClercq C, Johnson M, Joseph-McCarthy D, Ellingboe JW, Lin L, Nowak P, Presman E, Strand J, Tam A, Williams CM, Yao S, Tsao DH, Fitz LJ. Identification and characterization of acidic mammalian chitinase inhibitors. J Med Chem. 2010 Aug 26;53(16):6122-8. PMID:20666458 doi:10.1021/jm100533p

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3rm9"

Categories: Chitinase | Human | Large Structures | Olland, A | Hydrolase-hydrolase inhibitor complex

@@ Line 1: / Line 1: @@
 ==AMCase in complex with Compound 3==
-<StructureSection load='3rm9' size='340' side='right' caption='[[3rm9]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='3rm9' size='340' side='right'caption='[[3rm9]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3rm9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RM9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RM9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3rm9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RM9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RM9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=613:4-(4-CHLOROPHENYL)PIPERAZINE-1-CARBOXIMIDAMIDE'>613</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=613:4-(4-CHLOROPHENYL)PIPERAZINE-1-CARBOXIMIDAMIDE'>613</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rm4|3rm4]], [[3rm8|3rm8]], [[3rme|3rme]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3rm4|3rm4]], [[3rm8|3rm8]], [[3rme|3rme]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHIA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CHIA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Chitinase Chitinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.14 3.2.1.14] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rm9 OCA], [http://pdbe.org/3rm9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rm9 RCSB], [http://www.ebi.ac.uk/pdbsum/3rm9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rm9 ProSAT]</span></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=3rm9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rm9 OCA], [https://pdbe.org/3rm9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rm9 RCSB], [https://www.ebi.ac.uk/pdbsum/3rm9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rm9 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CHIA_HUMAN CHIA_HUMAN]] Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to IL-13 and inflammation in response to IL-13. Stimulates chemokine production by pulmonary epithelial cells. Protects lung epithelial cells against apoptosis and promotes phosphorylation of AKT1. Its function in the inflammatory response and in protecting cells against apoptosis is inhibited by allosamidin, suggesting that the function of this protein depends on carbohydrate binding.<ref>PMID:11085997</ref> <ref>PMID:18824549</ref> <ref>PMID:19342690</ref> <ref>PMID:19435888</ref>
+[[https://www.uniprot.org/uniprot/CHIA_HUMAN CHIA_HUMAN]] Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to IL-13 and inflammation in response to IL-13. Stimulates chemokine production by pulmonary epithelial cells. Protects lung epithelial cells against apoptosis and promotes phosphorylation of AKT1. Its function in the inflammatory response and in protecting cells against apoptosis is inhibited by allosamidin, suggesting that the function of this protein depends on carbohydrate binding.<ref>PMID:11085997</ref> <ref>PMID:18824549</ref> <ref>PMID:19342690</ref> <ref>PMID:19435888</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 ==See Also==
-*[[Chitinase|Chitinase]]
+*[[Chitinase 3D structures|Chitinase 3D structures]]
 == References ==
 <references/>
@@ Line 30: / Line 30: @@
 [[Category: Chitinase]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Olland, A]]
 [[Category: Hydrolase-hydrolase inhibitor complex]]

3rm9

From Proteopedia

Revision as of 10:16, 22 June 2022

AMCase in complex with Compound 3

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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