6hgy

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE OF CATHEPSIN K WITH N-DESMETHYL THALASSOSPIRAMIDE C

Structural highlights

6hgy 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 2.2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CATK_HUMAN Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:265800. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature.^[1] ^[2] ^[3] ^[4]

Function

CATK_HUMAN Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation.

Publication Abstract from PubMed

A total synthesis of N-desmethyl thalassospiramide C, a unique strained macrocyclic proteobacterial depsipeptide, enabled a detailed crystallographic study of its covalent complex with cathepsin K, a member of a medicinally important family of cysteine proteases. The study provides support for the mechanism of action, and the insight gained can be used for structure-based drug design targeting these calpain proteases.

Total Synthesis of Covalent Cysteine Protease Inhibitor N-Desmethyl Thalassospiramide C and Crystallographic Evidence for Its Mode of Action.,Fournier J, Chen K, Mailyan AK, Jackson JJ, Buckman BO, Emayan K, Yuan S, Rajagopalan R, Misialek S, Adler M, Blaesse M, Griessner A, Zakarian A Org Lett. 2019 Jan 18;21(2):508-512. doi: 10.1021/acs.orglett.8b03821. Epub 2019 , Jan 10. PMID:30628449^[5]

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

References

↑ Gelb BD, Shi GP, Chapman HA, Desnick RJ. Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science. 1996 Aug 30;273(5279):1236-8. PMID:8703060
↑ Gelb BD, Willner JP, Dunn TM, Kardon NB, Verloes A, Poncin J, Desnick RJ. Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a patient with pycnodysostosis. Am J Hum Genet. 1998 Apr;62(4):848-54. PMID:9529353 doi:S0002-9297(07)60977-X
↑ Ho N, Punturieri A, Wilkin D, Szabo J, Johnson M, Whaley J, Davis J, Clark A, Weiss S, Francomano C. Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K protein. J Bone Miner Res. 1999 Oct;14(10):1649-53. PMID:10491211
↑ Haagerup A, Hertz JM, Christensen MF, Binderup H, Kruse TA. Cathepsin K gene mutations and 1q21 haplotypes in at patients with pycnodysostosis in an outbred population. Eur J Hum Genet. 2000 Jun;8(6):431-6. PMID:10878663 doi:10.1038/sj.ejhg.5200481
↑ Fournier J, Chen K, Mailyan AK, Jackson JJ, Buckman BO, Emayan K, Yuan S, Rajagopalan R, Misialek S, Adler M, Blaesse M, Griessner A, Zakarian A. Total Synthesis of Covalent Cysteine Protease Inhibitor N-Desmethyl Thalassospiramide C and Crystallographic Evidence for Its Mode of Action. Org Lett. 2019 Jan 18;21(2):508-512. doi: 10.1021/acs.orglett.8b03821. Epub 2019 , Jan 10. PMID:30628449 doi:http://dx.doi.org/10.1021/acs.orglett.8b03821

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6hgy"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6hgy is ON HOLD  until Aug 23 2020
+==CRYSTAL STRUCTURE OF CATHEPSIN K WITH N-DESMETHYL THALASSOSPIRAMIDE C==
+<StructureSection load='6hgy' size='340' side='right'caption='[[6hgy]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6hgy]] 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=6HGY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HGY 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]] 2.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G4B:(~{Z})-~{N}-[(2~{S})-3-(4-hydroxyphenyl)-1-[[(2~{S})-1-[[(3~{S},6~{S},11~{R})-3-[(4-hydroxyphenyl)methyl]-2,5,8-tris(oxidanylidene)-6-propan-2-yl-1-oxa-4,7-diazacyclododec-11-yl]amino]-3-methyl-1-oxidanylidene-butan-2-yl]amino]-1-oxidanylidene-propan-2-yl]dec-3-enamide'>G4B</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=6hgy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hgy OCA], [https://pdbe.org/6hgy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hgy RCSB], [https://www.ebi.ac.uk/pdbsum/6hgy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hgy ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN] Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:[https://omim.org/entry/265800 265800]. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature.<ref>PMID:8703060</ref> <ref>PMID:9529353</ref> <ref>PMID:10491211</ref> <ref>PMID:10878663</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/CATK_HUMAN CATK_HUMAN] Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A total synthesis of N-desmethyl thalassospiramide C, a unique strained macrocyclic proteobacterial depsipeptide, enabled a detailed crystallographic study of its covalent complex with cathepsin K, a member of a medicinally important family of cysteine proteases. The study provides support for the mechanism of action, and the insight gained can be used for structure-based drug design targeting these calpain proteases.
-Authors:
+Total Synthesis of Covalent Cysteine Protease Inhibitor N-Desmethyl Thalassospiramide C and Crystallographic Evidence for Its Mode of Action.,Fournier J, Chen K, Mailyan AK, Jackson JJ, Buckman BO, Emayan K, Yuan S, Rajagopalan R, Misialek S, Adler M, Blaesse M, Griessner A, Zakarian A Org Lett. 2019 Jan 18;21(2):508-512. doi: 10.1021/acs.orglett.8b03821. Epub 2019 , Jan 10. PMID:30628449<ref>PMID:30628449</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6hgy" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Cathepsin 3D structures|Cathepsin 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Adler M]]
+[[Category: Blaesse M]]
+[[Category: Buckman BO]]
+[[Category: Griessner A]]
+[[Category: Zakarian A]]

6hgy

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF CATHEPSIN K WITH N-DESMETHYL THALASSOSPIRAMIDE C

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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