1h6v: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1h6v.gif|left|200px]] | [[Image:1h6v.gif|left|200px]] | ||
'''MAMMALIAN THIOREDOXIN REDUCTASE''' | {{Structure | ||
|PDB= 1h6v |SIZE=350|CAPTION= <scene name='initialview01'>1h6v</scene>, resolution 3.0Å | |||
|SITE= <scene name='pdbsite=FAA:Fad+Binding+Site+For+Chain+A'>FAA</scene>, <scene name='pdbsite=FAB:Fad+Binding+Site+For+Chain+B'>FAB</scene>, <scene name='pdbsite=FAC:Fad+Binding+Site+For+Chain+C'>FAC</scene>, <scene name='pdbsite=FAD:Fad+Binding+Site+For+Chain+D'>FAD</scene>, <scene name='pdbsite=FAE:Fad+Binding+Site+For+Chain+E'>FAE</scene>, <scene name='pdbsite=FAF:Fad+Binding+Site+For+Chain+F'>FAF</scene>, <scene name='pdbsite=NDA:Ndp+Binding+Site+For+Chain+A'>NDA</scene>, <scene name='pdbsite=NDB:Ndp+Binding+Site+For+Chain+B'>NDB</scene>, <scene name='pdbsite=NDC:Ndp+Binding+Site+For+Chain+C'>NDC</scene>, <scene name='pdbsite=NDD:Ndp+Binding+Site+For+Chain+D'>NDD</scene>, <scene name='pdbsite=NDE:Ndp+Binding+Site+For+Chain+E'>NDE</scene> and <scene name='pdbsite=NDF:Ndp+Binding+Site+For+Chain+F'>NDF</scene> | |||
|LIGAND= <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene> and <scene name='pdbligand=NDP:NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE'>NDP</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Transferred_entry:_1.8.1.9 Transferred entry: 1.8.1.9], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.4.5 1.6.4.5] | |||
|GENE= | |||
}} | |||
'''MAMMALIAN THIOREDOXIN REDUCTASE''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
1H6V is a [ | 1H6V is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H6V OCA]. | ||
==Reference== | ==Reference== | ||
Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme., Sandalova T, Zhong L, Lindqvist Y, Holmgren A, Schneider G, Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9533-8. Epub 2001 Jul 31. PMID:[http:// | Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme., Sandalova T, Zhong L, Lindqvist Y, Holmgren A, Schneider G, Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9533-8. Epub 2001 Jul 31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11481439 11481439] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 24: | Line 33: | ||
[[Category: pyridine nucleotide-disulfide oxidoreductase]] | [[Category: pyridine nucleotide-disulfide oxidoreductase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:33:04 2008'' | ||
Revision as of 12:33, 20 March 2008
| |||||||
| , resolution 3.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , , , , , , , , , and | ||||||
| Ligands: | and | ||||||
| Activity: | Transferred entry: 1.8.1.9, with EC number 1.6.4.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
MAMMALIAN THIOREDOXIN REDUCTASE
OverviewOverview
Thioredoxin reductases (TrxRs) from mammalian cells contain an essential selenocysteine residue in the conserved C-terminal sequence Gly-Cys-SeCys-Gly forming a selenenylsulfide in the oxidized enzyme. Reduction by NADPH generates a selenolthiol, which is the active site in reduction of Trx. The three-dimensional structure of the SeCys498Cys mutant of rat TrxR in complex with NADP(+) has been determined to 3.0-A resolution by x-ray crystallography. The overall structure is similar to that of glutathione reductase (GR), including conserved amino acid residues binding the cofactors FAD and NADPH. Surprisingly, all residues directly interacting with the substrate glutathione disulfide in GR are conserved despite the failure of glutathione disulfide to act as a substrate for TrxR. The 16-residue C-terminal tail, which is unique to mammalian TrxR, folds in such a way that it can approach the active site disulfide of the other subunit in the dimer. A model of the complex of TrxR with Trx suggests that electron transfer from NADPH to the disulfide of the substrate is possible without large conformational changes. The C-terminal extension typical of mammalian TrxRs has two functions: (i) it extends the electron transport chain from the catalytic disulfide to the enzyme surface, where it can react with Trx, and (ii) it prevents the enzyme from acting as a GR by blocking the redox-active disulfide. Our results suggest that mammalian TrxR evolved from the GR scaffold rather than from its prokaryotic counterpart. This evolutionary switch renders cell growth dependent on selenium.
About this StructureAbout this Structure
1H6V is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
ReferenceReference
Three-dimensional structure of a mammalian thioredoxin reductase: implications for mechanism and evolution of a selenocysteine-dependent enzyme., Sandalova T, Zhong L, Lindqvist Y, Holmgren A, Schneider G, Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9533-8. Epub 2001 Jul 31. PMID:11481439
Page seeded by OCA on Thu Mar 20 11:33:04 2008