6jkh

From Proteopedia

(Difference between revisions)

Current revision

The NAD+-bound form of human NSDHL

Structural highlights

6jkh is a 2 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 3Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

NSDHL_HUMAN CHILD syndrome;CK syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

NSDHL_HUMAN Involved in the sequential removal of two C-4 methyl groups in post-squalene cholesterol biosynthesis.^[1]

Publication Abstract from PubMed

NAD(P)-dependent steroid dehydrogenase-like (NSDHL), an essential enzyme in human cholesterol synthesis and a regulator of epidermal growth factor receptor (EGFR) trafficking pathways, has attracted interest as a therapeutic target due to its crucial relevance to cholesterol-related diseases and carcinomas. However, the development of pharmacological agents for targeting NSDHL has been hindered by the absence of the atomic details of NSDHL. In this study, we reported two X-ray crystal structures of human NSDHL, which revealed a detailed description of the coenzyme-binding site and the unique conformational change upon the binding of a coenzyme. A structure-based virtual screening and biochemical evaluation were performed and identified a novel inhibitor for NSDHL harboring suppressive activity towards EGFR. In EGFR-driven human cancer cells, treatment with the potent NSDHL inhibitor enhanced the antitumor effect of an EGFR kinase inhibitor. Overall, these findings could serve as good platforms for the development of therapeutic agents against NSDHL-related diseases.

Crystal structures of human NSDHL and development of its novel inhibitor with the potential to suppress EGFR activity.,Kim DG, Cho S, Lee KY, Cheon SH, Yoon HJ, Lee JY, Kim D, Shin KS, Koh CH, Koo JS, Choi Y, Lee HH, Oh YK, Jeong YS, Chung SJ, Baek M, Jung KY, Lim HJ, Kim HS, Park SJ, Lee JY, Lee SJ, Lee BJ Cell Mol Life Sci. 2020 Mar 5. pii: 10.1007/s00018-020-03490-2. doi:, 10.1007/s00018-020-03490-2. PMID:32140747^[2]

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

References

↑ Caldas H, Herman GE. NSDHL, an enzyme involved in cholesterol biosynthesis, traffics through the Golgi and accumulates on ER membranes and on the surface of lipid droplets. Hum Mol Genet. 2003 Nov 15;12(22):2981-91. doi: 10.1093/hmg/ddg321. Epub 2003 Sep, 23. PMID:14506130 doi:http://dx.doi.org/10.1093/hmg/ddg321
↑ Kim DG, Cho S, Lee KY, Cheon SH, Yoon HJ, Lee JY, Kim D, Shin KS, Koh CH, Koo JS, Choi Y, Lee HH, Oh YK, Jeong YS, Chung SJ, Baek M, Jung KY, Lim HJ, Kim HS, Park SJ, Lee JY, Lee SJ, Lee BJ. Crystal structures of human NSDHL and development of its novel inhibitor with the potential to suppress EGFR activity. Cell Mol Life Sci. 2020 Mar 5. pii: 10.1007/s00018-020-03490-2. doi:, 10.1007/s00018-020-03490-2. PMID:32140747 doi:http://dx.doi.org/10.1007/s00018-020-03490-2

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

Categories: Homo sapiens | Large Structures | Kim D | Lee B | Lee SJ

@@ Line 1: / Line 1: @@
-==cholesterol-decarboxylating enzyme 2==
+==The NAD+-bound form of human NSDHL==
 <StructureSection load='6jkh' size='340' side='right'caption='[[6jkh]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6jkh]] 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=6JKH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6JKH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6jkh]] is a 2 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=6JKH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JKH FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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]] 3&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NSDHL, H105E3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-beta-hydroxysteroid-4-alpha-carboxylate_3-dehydrogenase_(decarboxylating) 3-beta-hydroxysteroid-4-alpha-carboxylate 3-dehydrogenase (decarboxylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.170 1.1.1.170] </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=6jkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jkh OCA], [https://pdbe.org/6jkh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jkh RCSB], [https://www.ebi.ac.uk/pdbsum/6jkh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jkh ProSAT]</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=6jkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jkh OCA], [http://pdbe.org/6jkh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6jkh RCSB], [http://www.ebi.ac.uk/pdbsum/6jkh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6jkh ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/NSDHL_HUMAN NSDHL_HUMAN]] CHILD syndrome;CK syndrome. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/NSDHL_HUMAN NSDHL_HUMAN] CHILD syndrome;CK syndrome. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/NSDHL_HUMAN NSDHL_HUMAN]] Involved in the sequential removal of two C-4 methyl groups in post-squalene cholesterol biosynthesis.<ref>PMID:14506130</ref>
+[https://www.uniprot.org/uniprot/NSDHL_HUMAN NSDHL_HUMAN] Involved in the sequential removal of two C-4 methyl groups in post-squalene cholesterol biosynthesis.<ref>PMID:14506130</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Kim, D]]
+[[Category: Kim D]]
-[[Category: Lee, B]]
+[[Category: Lee B]]
-[[Category: Lee, S J]]
+[[Category: Lee SJ]]
-[[Category: Cholesterol]]
-[[Category: Dehydrogenase]]
-[[Category: Oxidoreductase]]

6jkh

From Proteopedia

Current revision

The NAD+-bound form of human NSDHL

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox