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| - | [[Image:2pfg.jpg|left|200px]] | |
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| - | {{Structure
| + | ==Crystal structure of human CBR1 in complex with BiGF2.== |
| - | |PDB= 2pfg |SIZE=350|CAPTION= <scene name='initialview01'>2pfg</scene>, resolution 1.54Å
| + | <StructureSection load='2pfg' size='340' side='right'caption='[[2pfg]], [[Resolution|resolution]] 1.54Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=DDD:(5R,10S)-5-{[(CARBOXYMETHYL)AMINO]CARBONYL}-7-OXO-3-THIA-1,6-DIAZABICYCLO[4.4.1]UNDECANE-10-CARBOXYLIC+ACID'>DDD</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
| + | <table><tr><td colspan='2'>[[2pfg]] 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=2PFG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PFG FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.54Å</td></tr> |
| - | |GENE= CBR1, CBR, CRN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DDD:(5R,10S)-5-{[(CARBOXYMETHYL)AMINO]CARBONYL}-7-OXO-3-THIA-1,6-DIAZABICYCLO[4.4.1]UNDECANE-10-CARBOXYLIC+ACID'>DDD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=M0H:S-(HYDROXYMETHYL)-L-CYSTEINE'>M0H</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=2pfg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pfg OCA], [https://pdbe.org/2pfg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pfg RCSB], [https://www.ebi.ac.uk/pdbsum/2pfg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pfg ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CBR1_HUMAN CBR1_HUMAN] NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E2 to prostaglandin F2-alpha. Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione.<ref>PMID:18449627</ref> <ref>PMID:15799708</ref> <ref>PMID:17912391</ref> <ref>PMID:18826943</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pf/2pfg_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2pfg ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Glutathione forms complex reaction products with formaldehyde, which can be further modified through enzymatic modification. We studied the non-enzymatic reaction between glutathione and formaldehyde and identified a bicyclic complex containing two equivalents of formaldehyde and one glutathione molecule by protein X-ray crystallography (PDB accession number 2PFG). We have also used (1)H, (13)C and 2D NMR spectroscopy to confirm the structure of this unusual adduct. The key feature of this adduct is the involvement of the gamma-glutamyl alpha-amine and the Cys thiol in the formation of the bicyclic ring structure. These findings suggest that the structure of GSH allows for bi-dentate masking of the reactivity of formaldehyde. As this species predominates at near physiological pH values, we suggest this adduct may have biological significance. |
| | | | |
| - | '''Crystal structure of human CBR1 in complex with BiGF2.'''
| + | Glutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane adduct.,Bateman R, Rauh D, Shokat KM Org Biomol Chem. 2007 Oct 21;5(20):3363-7. Epub 2007 Aug 29. PMID:17912391<ref>PMID:17912391</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 2pfg" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Overview== | + | ==See Also== |
| - | Glutathione forms complex reaction products with formaldehyde, which can be further modified through enzymatic modification. We studied the non-enzymatic reaction between glutathione and formaldehyde and identified a bicyclic complex containing two equivalents of formaldehyde and one glutathione molecule by protein X-ray crystallography (PDB accession number 2PFG). We have also used (1)H, (13)C and 2D NMR spectroscopy to confirm the structure of this unusual adduct. The key feature of this adduct is the involvement of the gamma-glutamyl alpha-amine and the Cys thiol in the formation of the bicyclic ring structure. These findings suggest that the structure of GSH allows for bi-dentate masking of the reactivity of formaldehyde. As this species predominates at near physiological pH values, we suggest this adduct may have biological significance.
| + | *[[Carbonyl reductase 3D structures|Carbonyl reductase 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure==
| + | <references/> |
| - | 2PFG is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PFG OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference== | + | |
| - | Glutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane adduct., Bateman R, Rauh D, Shokat KM, Org Biomol Chem. 2007 Oct 21;5(20):3363-7. Epub 2007 Aug 29. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17912391 17912391]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Bateman, R L.]] | + | [[Category: Bateman RL]] |
| - | [[Category: Rauh, D.]] | + | [[Category: Rauh D]] |
| - | [[Category: Shokat, K M.]] | + | [[Category: Shokat KM]] |
| - | [[Category: CL]]
| + | |
| - | [[Category: DDD]]
| + | |
| - | [[Category: GOL]]
| + | |
| - | [[Category: NAP]]
| + | |
| - | [[Category: glutathione]]
| + | |
| - | [[Category: macro molecule]]
| + | |
| - | [[Category: oxidoreductase]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:12:18 2008''
| + | |
| Structural highlights
2pfg 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 1.54Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
CBR1_HUMAN NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E2 to prostaglandin F2-alpha. Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Glutathione forms complex reaction products with formaldehyde, which can be further modified through enzymatic modification. We studied the non-enzymatic reaction between glutathione and formaldehyde and identified a bicyclic complex containing two equivalents of formaldehyde and one glutathione molecule by protein X-ray crystallography (PDB accession number 2PFG). We have also used (1)H, (13)C and 2D NMR spectroscopy to confirm the structure of this unusual adduct. The key feature of this adduct is the involvement of the gamma-glutamyl alpha-amine and the Cys thiol in the formation of the bicyclic ring structure. These findings suggest that the structure of GSH allows for bi-dentate masking of the reactivity of formaldehyde. As this species predominates at near physiological pH values, we suggest this adduct may have biological significance.
Glutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane adduct.,Bateman R, Rauh D, Shokat KM Org Biomol Chem. 2007 Oct 21;5(20):3363-7. Epub 2007 Aug 29. PMID:17912391[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gonzalez-Covarrubias V, Kalabus JL, Blanco JG. Inhibition of polymorphic human carbonyl reductase 1 (CBR1) by the cardioprotectant flavonoid 7-monohydroxyethyl rutoside (monoHER). Pharm Res. 2008 Jul;25(7):1730-4. doi: 10.1007/s11095-008-9592-5. Epub 2008 May, 1. PMID:18449627 doi:http://dx.doi.org/10.1007/s11095-008-9592-5
- ↑ Tanaka M, Bateman R, Rauh D, Vaisberg E, Ramachandani S, Zhang C, Hansen KC, Burlingame AL, Trautman JK, Shokat KM, Adams CL. An unbiased cell morphology-based screen for new, biologically active small molecules. PLoS Biol. 2005 May;3(5):e128. Epub 2005 Apr 5. PMID:15799708 doi:10.1371/journal.pbio.0030128
- ↑ Bateman R, Rauh D, Shokat KM. Glutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane adduct. Org Biomol Chem. 2007 Oct 21;5(20):3363-7. Epub 2007 Aug 29. PMID:17912391 doi:10.1039/b707602a
- ↑ Bateman RL, Rauh D, Tavshanjian B, Shokat KM. Human carbonyl reductase 1 is an S-nitrosoglutathione reductase. J Biol Chem. 2008 Dec 19;283(51):35756-62. Epub 2008 Sep 29. PMID:18826943 doi:10.1074/jbc.M807125200
- ↑ Bateman R, Rauh D, Shokat KM. Glutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane adduct. Org Biomol Chem. 2007 Oct 21;5(20):3363-7. Epub 2007 Aug 29. PMID:17912391 doi:10.1039/b707602a
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