View source for 6mv2


==2.05A resolution structure of the CS-b5R domains of human Ncb5or (NADP+ form)==
<StructureSection load='6mv2' size='340' side='right'caption='[[6mv2]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6mv2]] 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=6MV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MV2 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]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=6mv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mv2 OCA], [https://pdbe.org/6mv2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mv2 RCSB], [https://www.ebi.ac.uk/pdbsum/6mv2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mv2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NB5R4_HUMAN NB5R4_HUMAN] NADH-cytochrome b5 reductase involved in endoplasmic reticulum stress response pathway. Plays a critical role in protecting pancreatic beta-cells against oxidant stress, possibly by protecting the cell from excess buildup of reactive oxygen species (ROS). Reduces a variety of substrates in vitro, such as cytochrome c, feericyanide and methemoglobin.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ncb5or (NADH-cytochrome b5 oxidoreductase), a cytosolic ferric reductase implicated in diabetes and neurological diseases, comprises three distinct domains, cytochrome b5 (b5) and cytochrome b5 reductase (b5R) domains separated by a CHORD-Sgt1 (CS) domain, and a novel 50-residue N-terminal region. Understanding how interdomain interactions in Ncb5or facilitate the shuttling of electrons from NAD(P)H to heme, and how the process compares with the microsomal b5 (Cyb5A) and b5R (Cyb5R3) system, is of interest. A high-resolution structure of the b5 domain (PDB entry 3lf5) has previously been reported, which exhibits substantial differences in comparison to Cyb5A. The structural characterization of a construct comprising the naturally fused CS and b5R domains with bound FAD and NAD(+) (PDB entry 6mv1) or NADP(+) (PDB entry 6mv2) is now reported. The structures reveal that the linker between the CS and b5R cores is more ordered than predicted, with much of it extending the beta-sandwich motif of the CS domain. This limits the flexibility between the two domains, which recognize one another via a short beta-sheet motif and a network of conserved side-chain hydrogen bonds, salt bridges and cation-pi interactions. Notable differences in FAD-protein interactions in Ncb5or and Cyb5R3 provide insight into the selectivity for docking of their respective b5 redox partners. The structures also afford a structural explanation for the unusual ability of Ncb5or to utilize both NADH and NADPH, and represent the first examples of native, fully oxidized b5R family members in which the nicotinamide ring of NAD(P)(+) resides in the active site. Finally, the structures, together with sequence alignments, show that the b5R domain is more closely related to single-domain Cyb5R proteins from plants, fungi and some protists than to Cyb5R3 from animals.

Crystal structures of the naturally fused CS and cytochrome b5 reductase (b5R) domains of Ncb5or reveal an expanded CS fold, extensive CS-b5R interactions and productive binding of the NAD(P)(+) nicotinamide ring.,Benson DR, Lovell S, Mehzabeen N, Galeva N, Cooper A, Gao P, Battaile KP, Zhu H Acta Crystallogr D Struct Biol. 2019 Jul 1;75(Pt 7):628-638. doi:, 10.1107/S205979831900754X. Epub 2019 Jun 26. PMID:31282472<ref>PMID:31282472</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6mv2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Battaile KP]]
[[Category: Benson DR]]
[[Category: Cooper A]]
[[Category: Gao P]]
[[Category: Lovell S]]
[[Category: Mehzabeen N]]
[[Category: Zhu H]]