This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


4o12

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:36, 1 March 2024) (edit) (undo)
 
(One intermediate revision not shown.)
Line 3: Line 3:
<StructureSection load='4o12' size='340' side='right'caption='[[4o12]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='4o12' size='340' side='right'caption='[[4o12]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[4o12]] 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=4O12 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O12 FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[4o12]] 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=4O12 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O12 FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2QG:2-[6-(4-CHLOROPHENOXY)HEXYL]-1-CYANO-3-PYRIDIN-4-YLGUANIDINE'>2QG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.498&#8491;</td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4o0z|4o0z]], [[4o10|4o10]]</td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2QG:2-[6-(4-CHLOROPHENOXY)HEXYL]-1-CYANO-3-PYRIDIN-4-YLGUANIDINE'>2QG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NAMPT, PBEF, PBEF1 ([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=4o12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o12 OCA], [https://pdbe.org/4o12 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o12 RCSB], [https://www.ebi.ac.uk/pdbsum/4o12 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o12 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/Nicotinamide_phosphoribosyltransferase Nicotinamide phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.12 2.4.2.12] </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=4o12 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o12 OCA], [http://pdbe.org/4o12 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o12 RCSB], [http://www.ebi.ac.uk/pdbsum/4o12 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o12 ProSAT]</span></td></tr>
+
</table>
</table>
== Function ==
== Function ==
-
[[http://www.uniprot.org/uniprot/NAMPT_HUMAN NAMPT_HUMAN]] Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway (By similarity).
+
[https://www.uniprot.org/uniprot/NAMPT_HUMAN NAMPT_HUMAN] Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway (By similarity).
-
<div style="background-color:#fffaf0;">
+
-
== Publication Abstract from PubMed ==
+
-
Prolonged inhibition of nicotinamide phosphoribosyltransferase (NAMPT) is a strategy for targeting cancer metabolism. Many NAMPT inhibitors undergo NAMPT-catalyzed phosphoribosylation (pRib), a property often correlated with their cellular potency. To understand this phenomenon and facilitate drug design, we analyzed a potent cellularly active NAMPT inhibitor (GNE-617). A crystal structure of pRib-GNE-617 in complex with NAMPT protein revealed a relaxed binding mode. Consistently, the adduct formation resulted in tight binding and strong product inhibition. In contrast, a biochemically equipotent isomer of GNE-617 (GNE-643) also formed pRib adducts but displayed significantly weaker cytotoxicity. Structural analysis revealed an altered ligand conformation of GNE-643, thus suggesting weak association of the adducts with NAMPT. Our data support a model for cellularly active NAMPT inhibitors that undergo NAMPT-catalyzed phosphoribosylation to produce pRib adducts that retain efficient binding to the enzyme.
+
-
 
+
-
Structural and biochemical analyses of the catalysis and potency impact of inhibitor phosphoribosylation by human nicotinamide phosphoribosyltransferase.,Oh A, Ho YC, Zak M, Liu Y, Chen X, Yuen PW, Zheng X, Liu Y, Dragovich PS, Wang W Chembiochem. 2014 May 26;15(8):1121-30. doi: 10.1002/cbic.201402023. Epub 2014, May 5. PMID:24797455<ref>PMID:24797455</ref>
+
-
 
+
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 4o12" style="background-color:#fffaf0;"></div>
+
==See Also==
==See Also==
-
*[[Phosphoribosyltransferase|Phosphoribosyltransferase]]
+
*[[Phosphoribosyltransferase 3D structures|Phosphoribosyltransferase 3D structures]]
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Human]]
+
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Nicotinamide phosphoribosyltransferase]]
+
[[Category: Oh A]]
-
[[Category: Oh, A]]
+
[[Category: Wang W]]
-
[[Category: Wang, W]]
+
-
[[Category: Transferase-transferase inhibitor complex]]
+

Current revision

Structural and Biochemical Analyses of the Catalysis and Potency Impact of Inhibitor Phosphoribosylation by Human Nicotinamide Phosphoribosyltransferase

PDB ID 4o12

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4o12"
Personal tools