1sqt

From Proteopedia

(Difference between revisions)

Current revision

Substituted 2-Naphthamidine Inhibitors of Urokinase

Structural highlights

1sqt 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.
Method:	X-ray diffraction, Resolution 1.9Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

UROK_HUMAN Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:601709. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.^[1]

Function

UROK_HUMAN Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.

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

Several 8-substituted 2-naphthamidine-based inhibitors of the serine protease urokinase plasminogen activator (uPA) are described. Direct attachment of five-membered saturated or unsaturated rings improved inhibitor performance; substitution with sulfones further improved binding profiles. Combination of these substituents or of previously described NH-linked heteroaromatic rings with 6-phenyl amide substituents provided further enhancements to potency and selectivity.

Interaction with the S1 beta-pocket of urokinase: 8-heterocycle substituted and 6,8-disubstituted 2-naphthamidine urokinase inhibitors.,Wendt MD, Geyer A, McClellan WJ, Rockway TW, Weitzberg M, Zhao X, Mantei R, Stewart K, Nienaber V, Klinghofer V, Giranda VL Bioorg Med Chem Lett. 2004 Jun 21;14(12):3063-8. PMID:15149645^[2]

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

References

↑ Paterson AD, Rommens JM, Bharaj B, Blavignac J, Wong I, Diamandis M, Waye JS, Rivard GE, Hayward CP. Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. Blood. 2010 Feb 11;115(6):1264-6. doi: 10.1182/blood-2009-07-233965. Epub 2009, Dec 9. PMID:20007542 doi:10.1182/blood-2009-07-233965
↑ Wendt MD, Geyer A, McClellan WJ, Rockway TW, Weitzberg M, Zhao X, Mantei R, Stewart K, Nienaber V, Klinghofer V, Giranda VL. Interaction with the S1 beta-pocket of urokinase: 8-heterocycle substituted and 6,8-disubstituted 2-naphthamidine urokinase inhibitors. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3063-8. PMID:15149645 doi:10.1016/j.bmcl.2004.04.030

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1sqt"

@@ Line 1: / Line 1: @@
 ==Substituted 2-Naphthamidine Inhibitors of Urokinase==
-<StructureSection load='1sqt' size='340' side='right' caption='[[1sqt]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='1sqt' size='340' side='right'caption='[[1sqt]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1sqt]] is a 1 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=1SQT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1SQT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1sqt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SQT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SQT FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UI3:7-METHOXY-8-[1-(METHYLSULFONYL)-1H-PYRAZOL-4-YL]NAPHTHALENE-2-CARBOXIMIDAMIDE'>UI3</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1owd|1owd]], [[1owe|1owe]], [[1owh|1owh]], [[1owi|1owi]], [[1owj|1owj]], [[1owk|1owk]], [[1sqa|1sqa]], [[1sqo|1sqo]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UI3:7-METHOXY-8-[1-(METHYLSULFONYL)-1H-PYRAZOL-4-YL]NAPHTHALENE-2-CARBOXIMIDAMIDE'>UI3</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLAU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1sqt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sqt OCA], [https://pdbe.org/1sqt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sqt RCSB], [https://www.ebi.ac.uk/pdbsum/1sqt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sqt ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/U-plasminogen_activator U-plasminogen activator], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.73 3.4.21.73] </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=1sqt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sqt OCA], [http://pdbe.org/1sqt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1sqt RCSB], [http://www.ebi.ac.uk/pdbsum/1sqt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1sqt ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[http://omim.org/entry/601709 601709]]. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.<ref>PMID:20007542</ref>
+[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:[https://omim.org/entry/601709 601709]. QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins.<ref>PMID:20007542</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN]] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
+[https://www.uniprot.org/uniprot/UROK_HUMAN UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 19: / Line 17: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sq/1sqt_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 35: / Line 33: @@
 ==See Also==
-*[[Urokinase|Urokinase]]
+*[[Urokinase 3D Structures|Urokinase 3D Structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: U-plasminogen activator]]
+[[Category: Large Structures]]
-[[Category: Geyer, A]]
+[[Category: Geyer A]]
-[[Category: Giranda, V L]]
+[[Category: Giranda VL]]
-[[Category: Klinghofer, V]]
+[[Category: Klinghofer V]]
-[[Category: Mantei, R]]
+[[Category: Mantei R]]
-[[Category: McClellan, W J]]
+[[Category: McClellan WJ]]
-[[Category: Nienaber, V]]
+[[Category: Nienaber V]]
-[[Category: Rockway, T W]]
+[[Category: Rockway TW]]
-[[Category: Stewart, K]]
+[[Category: Stewart K]]
-[[Category: Weitzberg, M]]
+[[Category: Weitzberg M]]
-[[Category: Wendt, M D]]
+[[Category: Wendt MD]]
-[[Category: Zhang, X]]
+[[Category: Zhang X]]
-[[Category: Egf-like domain]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Kringle]]
-[[Category: Plasminogen activation]]
-[[Category: Serine protease]]

1sqt

From Proteopedia

Current revision

Substituted 2-Naphthamidine Inhibitors of Urokinase

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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