4u93

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of Hsp90-alpha N-domain Bound to the Inhibitor NVP-HSP990

Structural highlights

4u93 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 1.55Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HS90A_HUMAN Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.^[1] ^[2]

Publication Abstract from PubMed

Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from a commercial hit. The exploration of this series led to the selection of NVP-HSP990 as a development candidate.

Design, Structure-Activity Relationship, and in Vivo Characterization of the Development Candidate NVP-HSP990.,McBride CM, Levine B, Xia Y, Bellamacina C, Machajewski T, Gao Z, Renhowe P, Antonios-McCrea W, Barsanti P, Brinner K, Costales A, Doughan B, Lin X, Louie A, McKenna M, Mendenhall K, Poon D, Rico A, Wang M, Williams TE, Abrams T, Fong S, Hendrickson T, Lei D, Lin J, Menezes D, Pryer N, Taverna P, Xu Y, Zhou Y, Shafer CM J Med Chem. 2014 Nov 13;57(21):9124-9. doi: 10.1021/jm501107q. Epub 2014 Nov 4. PMID:25368984^[3]

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

References

↑ Martinez-Ruiz A, Villanueva L, Gonzalez de Orduna C, Lopez-Ferrer D, Higueras MA, Tarin C, Rodriguez-Crespo I, Vazquez J, Lamas S. S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8525-30. Epub 2005 Jun 3. PMID:15937123 doi:10.1073/pnas.0407294102
↑ Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE. Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem. 2001 May 11;276(19):15571-4. Epub 2001 Mar 23. PMID:11274138 doi:10.1074/jbc.C100055200
↑ McBride CM, Levine B, Xia Y, Bellamacina C, Machajewski T, Gao Z, Renhowe P, Antonios-McCrea W, Barsanti P, Brinner K, Costales A, Doughan B, Lin X, Louie A, McKenna M, Mendenhall K, Poon D, Rico A, Wang M, Williams TE, Abrams T, Fong S, Hendrickson T, Lei D, Lin J, Menezes D, Pryer N, Taverna P, Xu Y, Zhou Y, Shafer CM. Design, Structure-Activity Relationship, and in Vivo Characterization of the Development Candidate NVP-HSP990. J Med Chem. 2014 Nov 13;57(21):9124-9. doi: 10.1021/jm501107q. Epub 2014 Nov 4. PMID:25368984 doi:http://dx.doi.org/10.1021/jm501107q

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/4u93"

Categories: Homo sapiens | Large Structures | Bellamacina CR | Bussiere D | Shafer CM

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 4u93 is ON HOLD
+==Crystal Structure of Hsp90-alpha N-domain Bound to the Inhibitor NVP-HSP990==
+<StructureSection load='4u93' size='340' side='right'caption='[[4u93]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4u93]] 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=4U93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U93 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]] 1.55&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=990:(7R)-2-AMINO-7-[4-FLUORO-2-(6-METHOXYPYRIDIN-2-YL)PHENYL]-4-METHYL-7,8-DIHYDROPYRIDO[4,3-D]PYRIMIDIN-5(6H)-ONE'>990</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=4u93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u93 OCA], [https://pdbe.org/4u93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u93 RCSB], [https://www.ebi.ac.uk/pdbsum/4u93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u93 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from a commercial hit. The exploration of this series led to the selection of NVP-HSP990 as a development candidate.
-Authors: Bellamacina, C.R., Shafer, C.M., Bussiere, D.
+Design, Structure-Activity Relationship, and in Vivo Characterization of the Development Candidate NVP-HSP990.,McBride CM, Levine B, Xia Y, Bellamacina C, Machajewski T, Gao Z, Renhowe P, Antonios-McCrea W, Barsanti P, Brinner K, Costales A, Doughan B, Lin X, Louie A, McKenna M, Mendenhall K, Poon D, Rico A, Wang M, Williams TE, Abrams T, Fong S, Hendrickson T, Lei D, Lin J, Menezes D, Pryer N, Taverna P, Xu Y, Zhou Y, Shafer CM J Med Chem. 2014 Nov 13;57(21):9124-9. doi: 10.1021/jm501107q. Epub 2014 Nov 4. PMID:25368984<ref>PMID:25368984</ref>
-Description: Crystal Structure of Hsp90-alpha N-domain Bound to the Inhibitor NVP-HSP990
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4u93" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Heat Shock Protein structures|Heat Shock Protein structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bellamacina CR]]
+[[Category: Bussiere D]]
+[[Category: Shafer CM]]

4u93

From Proteopedia

Current revision

Crystal Structure of Hsp90-alpha N-domain Bound to the Inhibitor NVP-HSP990

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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