3bhj

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human Carbonyl Reductase 1 in complex with glutathione

Structural highlights

3bhj 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 1.77Å
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

Human carbonyl reductase 1 (hCBR1) is an NADPH-dependent short chain dehydrogenase/reductase with broad substrate specificity and is thought to be responsible for the in vivo reduction of quinones, prostaglandins, and other carbonyl-containing compounds including xenobiotics. In addition, hCBR1 possesses a glutathione binding site that allows for increased affinity toward GSH-conjugated molecules. It has been suggested that the GSH-binding site is near the active site; however, no structures with GSH or GSH conjugates have been reported. We have solved the x-ray crystal structures of hCBR1 and a substrate mimic in complex with GSH and the catalytically inert GSH conjugate hydroxymethylglutathione (HMGSH). The structures reveal the GSH-binding site and provide insight into the affinity determinants for GSH-conjugated substrates. We further demonstrate that the structural isostere of HMGSH, S-nitrosoglutathione, is an ideal hCBR1 substrate (Km = 30 microm, kcat = 450 min(-1)) with kinetic constants comparable with the best known hCBR1 substrates. Furthermore, we demonstrate that hCBR1 dependent GSNO reduction occurs in A549 lung adenocarcinoma cell lysates and suggest that hCBR1 may be involved in regulation of tissue levels of GSNO.

Human carbonyl reductase 1 is an S-nitrosoglutathione reductase.,Bateman RL, Rauh D, Tavshanjian B, Shokat KM J Biol Chem. 2008 Dec 19;283(51):35756-62. Epub 2008 Sep 29. PMID:18826943^[5]

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

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 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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3bhj"

Categories: Homo sapiens | Large Structures | Bateman RL | Rauh D | Shokat KM

@@ Line 1: / Line 1: @@
 ==Crystal structure of human Carbonyl Reductase 1 in complex with glutathione==
-<StructureSection load='3bhj' size='340' side='right' caption='[[3bhj]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
+<StructureSection load='3bhj' size='340' side='right'caption='[[3bhj]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3bhj]] is a 1 chain structure with 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=3BHJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BHJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3bhj]] 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=3BHJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BHJ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AB3:3-(4-AMINO-1-TERT-BUTYL-1H-PYRAZOLO[3,4-D]PYRIMIDIN-3-YL)PHENOL'>AB3</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.77&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wma|1wma]], [[2pfg|2pfg]], [[3bhi|3bhi]], [[3bhm|3bhm]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AB3:3-(4-AMINO-1-TERT-BUTYL-1H-PYRAZOLO[3,4-D]PYRIMIDIN-3-YL)PHENOL'>AB3</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CBR1, CBR, CRN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3bhj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bhj OCA], [https://pdbe.org/3bhj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bhj RCSB], [https://www.ebi.ac.uk/pdbsum/3bhj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bhj 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/Carbonyl_reductase_(NADPH) Carbonyl reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.184 1.1.1.184] </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=3bhj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bhj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bhj RCSB], [http://www.ebi.ac.uk/pdbsum/3bhj PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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/bh/3bhj_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bh/3bhj_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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=3bhj ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 29: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3bhj" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Carbonyl reductase|Carbonyl reductase]]
+*[[Carbonyl reductase 3D structures|Carbonyl reductase 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 37: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bateman, R L]]
+[[Category: Large Structures]]
-[[Category: Rauh, D]]
+[[Category: Bateman RL]]
-[[Category: Shokat, K M]]
+[[Category: Rauh D]]
-[[Category: Nadp]]
+[[Category: Shokat KM]]
-[[Category: Oxidoreductase]]

3bhj

From Proteopedia

Current revision

Crystal structure of human Carbonyl Reductase 1 in complex with glutathione

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox