1onz: Difference between revisions

Revision as of 23:38, 24 December 2014

Oxalyl-aryl-Amino Benzoic acid Inhibitors of PTP1B, compound 8b

Structural highlights

1onz is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	968
Related:	1nl9, 1nny, 1no6, 1nz7, 1ony
Gene:	PTPN1 OR PTP1B (Homo sapiens)
Activity:	Protein-tyrosine-phosphatase, with EC number 3.1.3.48
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[PTN1_HUMAN] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.^[1] ^[2]

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

Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.

Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B.,Liu G, Szczepankiewicz BG, Pei Z, Janowick DA, Xin Z, Hajduk PJ, Abad-Zapatero C, Liang H, Hutchins CW, Fesik SW, Ballaron SJ, Stashko MA, Lubben T, Mika AK, Zinker BA, Trevillyan JM, Jirousek MR J Med Chem. 2003 May 22;46(11):2093-103. PMID:12747781^[3]

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

References

↑ Nievergall E, Janes PW, Stegmayer C, Vail ME, Haj FG, Teng SW, Neel BG, Bastiaens PI, Lackmann M. PTP1B regulates Eph receptor function and trafficking. J Cell Biol. 2010 Dec 13;191(6):1189-203. doi: 10.1083/jcb.201005035. Epub 2010, Dec 6. PMID:21135139 doi:10.1083/jcb.201005035
↑ Krishnan N, Fu C, Pappin DJ, Tonks NK. H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal. 2011 Dec 13;4(203):ra86. doi: 10.1126/scisignal.2002329. PMID:22169477 doi:10.1126/scisignal.2002329
↑ Liu G, Szczepankiewicz BG, Pei Z, Janowick DA, Xin Z, Hajduk PJ, Abad-Zapatero C, Liang H, Hutchins CW, Fesik SW, Ballaron SJ, Stashko MA, Lubben T, Mika AK, Zinker BA, Trevillyan JM, Jirousek MR. Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B. J Med Chem. 2003 May 22;46(11):2093-103. PMID:12747781 doi:https://dx.doi.org/10.1021/jm0205696

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Nievergall E, Janes PW, Stegmayer C, Vail ME, Haj FG, Teng SW, Neel BG, Bastiaens PI, Lackmann M. PTP1B regulates Eph receptor function and trafficking. J Cell Biol. 2010 Dec 13;191(6):1189-203. doi: 10.1083/jcb.201005035. Epub 2010, Dec 6. PMID:21135139 doi:10.1083/jcb.201005035

[2] Krishnan N, Fu C, Pappin DJ, Tonks NK. H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal. 2011 Dec 13;4(203):ra86. doi: 10.1126/scisignal.2002329. PMID:22169477 doi:10.1126/scisignal.2002329

[3] Liu G, Szczepankiewicz BG, Pei Z, Janowick DA, Xin Z, Hajduk PJ, Abad-Zapatero C, Liang H, Hutchins CW, Fesik SW, Ballaron SJ, Stashko MA, Lubben T, Mika AK, Zinker BA, Trevillyan JM, Jirousek MR. Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B. J Med Chem. 2003 May 22;46(11):2093-103. PMID:12747781 doi:https://dx.doi.org/10.1021/jm0205696

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1onz]] is a 1 chain structure with 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=1ONZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ONZ FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=968:2-[(7-HYDROXY-NAPHTHALEN-1-YL)-OXALYL-AMINO]-BENZOIC+ACID'>968</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=968:2-[(7-HYDROXY-NAPHTHALEN-1-YL)-OXALYL-AMINO]-BENZOIC+ACID'>968</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nl9|1nl9]], [[1nny|1nny]], [[1no6|1no6]], [[1nz7|1nz7]], [[1ony|1ony]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nl9|1nl9]], [[1nny|1nny]], [[1no6|1no6]], [[1nz7|1nz7]], [[1ony|1ony]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN1 OR PTP1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN1 OR PTP1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1onz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1onz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1onz RCSB], [http://www.ebi.ac.uk/pdbsum/1onz PDBsum]</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=1onz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1onz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1onz RCSB], [http://www.ebi.ac.uk/pdbsum/1onz PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PTN1_HUMAN PTN1_HUMAN]] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.<ref>PMID:21135139</ref> <ref>PMID:22169477</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 36: / Line 38: @@
 [[Category: Homo sapiens]]
 [[Category: Protein-tyrosine-phosphatase]]
-[[Category: Abad-Zapatero, C.]]
+[[Category: Abad-Zapatero, C]]
-[[Category: Ballaron, S J.]]
+[[Category: Ballaron, S J]]
-[[Category: Fesik, S W.]]
+[[Category: Fesik, S W]]
-[[Category: Hadjuk, P J.]]
+[[Category: Hadjuk, P J]]
-[[Category: Hutchins, C W.]]
+[[Category: Hutchins, C W]]
-[[Category: Janowich, D A.]]
+[[Category: Janowich, D A]]
-[[Category: Jirousek, M R.]]
+[[Category: Jirousek, M R]]
-[[Category: Liang, H.]]
+[[Category: Liang, H]]
-[[Category: Liu, G.]]
+[[Category: Liu, G]]
-[[Category: Lubben, T.]]
+[[Category: Lubben, T]]
-[[Category: Mika, A K.]]
+[[Category: Mika, A K]]
-[[Category: Pei, Z.]]
+[[Category: Pei, Z]]
-[[Category: Stashko, M A.]]
+[[Category: Stashko, M A]]
-[[Category: Szczepankiewicz, B G.]]
+[[Category: Szczepankiewicz, B G]]
-[[Category: Trevillyan, J M.]]
+[[Category: Trevillyan, J M]]
-[[Category: Xin, Z.]]
+[[Category: Xin, Z]]
-[[Category: Zinker, B A.]]
+[[Category: Zinker, B A]]
 [[Category: Hydrolase]]
 [[Category: Oxalyl-aryl-benzoic acid compound with napthyl moiety anchor inhibitor]]
 [[Category: Protein tyrosine phosphatase]]

1onz: Difference between revisions

Revision as of 23:38, 24 December 2014

Oxalyl-aryl-Amino Benzoic acid Inhibitors of PTP1B, compound 8b

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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