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4qof

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Revision as of 13:46, 5 April 2017

Crystal structure of fmn quinone reductase 2 AT 1.55A

Structural highlights

4qof is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Activity:	Ribosyldihydronicotinamide dehydrogenase (quinone), with EC number 1.10.99.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NQO2_HUMAN] The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.^[1]

Publication Abstract from PubMed

Melatonin exerts its biological effects through at least two transmembrane G-protein-coupled receptors, MT1 and MT2, and a lower-affinity cytosolic binding site, designated MT3. MT3 has recently been identified as QR2 (quinone reductase 2) (EC 1.10.99.2) which is of significance since it links the antioxidant effects of melatonin to a mechanism of action. Initially, QR2 was believed to function analogously to QR1 in protecting cells from highly reactive quinones. However, recent studies indicate that QR2 may actually transform certain quinone substrates into more highly reactive compounds capable of causing cellular damage. Therefore it is hypothesized that inhibition of QR2 in certain cases may lead to protection of cells against these highly reactive species. Since melatonin is known to inhibit QR2 activity, but its binding site and mode of inhibition are not known, we determined the mechanism of inhibition of QR2 by melatonin and a series of melatonin and 5-hydroxytryptamine (serotonin) analogues, and we determined the X-ray structures of melatonin and 2-iodomelatonin in complex with QR2 to between 1.5 and 1.8 A (1 A=0.1 nm) resolution. Finally, the thermodynamic binding constants for melatonin and 2-iodomelatonin were determined by ITC (isothermal titration calorimetry). The kinetic results indicate that melatonin is a competitive inhibitor against N-methyldihydronicotinamide (K(i)=7.2 microM) and uncompetitive against menadione (K(i)=92 microM), and the X-ray structures shows that melatonin binds in multiple orientations within the active sites of the QR2 dimer as opposed to an allosteric site. These results provide new insights into the binding mechanisms of melatonin and analogues to QR2.

Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2.,Calamini B, Santarsiero BD, Boutin JA, Mesecar AD Biochem J. 2008 Jul 1;413(1):81-91. PMID:18254726^[2]

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

References

↑ Calamini B, Santarsiero BD, Boutin JA, Mesecar AD. Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. Biochem J. 2008 Jul 1;413(1):81-91. PMID:18254726 doi:10.1042/BJ20071373
↑ Calamini B, Santarsiero BD, Boutin JA, Mesecar AD. Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2. Biochem J. 2008 Jul 1;413(1):81-91. PMID:18254726 doi:10.1042/BJ20071373

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4qof"

@@ Line 1: / Line 1: @@
 ==Crystal structure of fmn quinone reductase 2 AT 1.55A==
 <StructureSection load='4qof' size='340' side='right' caption='[[4qof]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ribosyldihydronicotinamide_dehydrogenase_(quinone) Ribosyldihydronicotinamide dehydrogenase (quinone)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.10.99.2 1.10.99.2] </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=4qof FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qof OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qof RCSB], [http://www.ebi.ac.uk/pdbsum/4qof PDBsum]</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=4qof FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qof OCA], [http://pdbe.org/4qof PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qof RCSB], [http://www.ebi.ac.uk/pdbsum/4qof PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qof ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4qof" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4qof

From Proteopedia

Revision as of 13:46, 5 April 2017

Crystal structure of fmn quinone reductase 2 AT 1.55A

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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