User:Emma Ste.Marie/Sandbox 1: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 20: Line 20:
'''General:'''
'''General:'''
Three types of mTrxRs have been characterized: the cytosolic form TrxR1, the mitochondrial form TrxR2, and thioredoxin glutathione reductase (TGR) that is found in testes. TGR is a TrxR-glutathione reductase hybrid enzyme that possesses an N-terminal glutaredoxin-domain in addition to a C-terminal selenocysteine-containing redox centre[5]. Cytosolic mTrxR1s contain a C-terminal redox center with the sequence Xaa-Cys1-Cys2-Xaa (Cys-mTrxRs), or, Xaa-Cys-Sec-Xaa (Sec-mTrxRs)[6]. In contrast, mTrxR2s (the mitochondrial form), contain a C-terminal disulfide redox center with the sequence: Gly-Cys1-Gly-Gly-Gly-Lys-Cys2-Gly[6]. mTrxRs belong to a family of functional homodimeric pyridine nucleotide disulphide oxidoreductases with high homology to glutathione reductases (GRs) and lipoamide dehydrogenase (LipDH). The overall fold of mTrxR resembles other homodimeric pyridine nucleotide disulphide oxidoreductases[5]. mTrxRs function as head to tail homodimers, and each subunit contains a binding domain for FAD and NADPH, an interface domain, and a discrete active centre[6].  
Three types of mTrxRs have been characterized: the cytosolic form TrxR1, the mitochondrial form TrxR2, and thioredoxin glutathione reductase (TGR) that is found in testes. TGR is a TrxR-glutathione reductase hybrid enzyme that possesses an N-terminal glutaredoxin-domain in addition to a C-terminal selenocysteine-containing redox centre[5]. Cytosolic mTrxR1s contain a C-terminal redox center with the sequence Xaa-Cys1-Cys2-Xaa (Cys-mTrxRs), or, Xaa-Cys-Sec-Xaa (Sec-mTrxRs)[6]. In contrast, mTrxR2s (the mitochondrial form), contain a C-terminal disulfide redox center with the sequence: Gly-Cys1-Gly-Gly-Gly-Lys-Cys2-Gly[6]. mTrxRs belong to a family of functional homodimeric pyridine nucleotide disulphide oxidoreductases with high homology to glutathione reductases (GRs) and lipoamide dehydrogenase (LipDH). The overall fold of mTrxR resembles other homodimeric pyridine nucleotide disulphide oxidoreductases[5]. mTrxRs function as head to tail homodimers, and each subunit contains a binding domain for FAD and NADPH, an interface domain, and a discrete active centre[6].  
Several Pfam domains (described by The European Bioinformatics Institute (EMBL-EBI), links below) present in mTrxR1 include: a glutaredoxin domain, pyridine nucleotide-disulphide oxidoreductase domain, pyridine nucleotide-disulphide oxidoreductase dimerisation domain, and nucleotide phosphate-binding region.
 
'''Motifs and Domains''':
 
Several Pfam domains (described by The European Bioinformatics Institute (EMBL-EBI)) present in mTrxR1 include: a glutaredoxin domain, pyridine nucleotide-disulphide oxidoreductase domain, pyridine nucleotide-disulphide oxidoreductase dimerisation domain, and nucleotide phosphate-binding region.
Link to Pfam information on mTrxR1: [http://pfam.xfam.org/family/PF00462.23] [http://pfam.xfam.org/structure/3qfa]
 
CATH database classifies mTrxR1 as an Alpha Beta protein, with 3-Layer(bba) Sandwich architecture, and a FAD/NAD(P)-binding domain. It also contains an Enolase-like domain, and is considered a member of the Glutaredoxin homologous superfamily.
Link to CATH information on mTrxR1: [http://www.cathdb.info/pdb/3qfa]


[[Image:NtermRedox.png|1000px|right|thumb|PDB: 3QFA with features highlighted. N-terminal redox centre of mTrxR: green ribbons are one monomer of mTrxR1, and blue ribbons are the other monomer. the FAD cofactor is displayed in sticks. The N-terminal disulfide bond (Cys59-Cys64) is highlighted in yellow spheres.]]
[[Image:NtermRedox.png|1000px|right|thumb|PDB: 3QFA with features highlighted. N-terminal redox centre of mTrxR: green ribbons are one monomer of mTrxR1, and blue ribbons are the other monomer. the FAD cofactor is displayed in sticks. The N-terminal disulfide bond (Cys59-Cys64) is highlighted in yellow spheres.]]




Line 48: Line 54:
== Analogues ==
== Analogues ==


Human TrxR1 and GR share a high active site residue similarity at the cofactor and substrate binding sites as well as a similar reaction mechanism with respect to the reductive half-reaction[5]. The structural and functional characteristics of GR have been studied for many years, and detailed information on the mechanism is available[5]. In Sec-mTrxRs, the 8 membered selenosulfide ring acts as an internal substrate that receives electrons from the N-terminal disulfide once it is reduced by NADPH. In contrast, GR and LipDP are essentially truncated forms of mTrxR that do not contain the flexible C-terminal tail. Instead, GR and LipDH reduce external substrates such as oxidized glutathione and lipoic acid, respectively[6].
Human TrxR1 and GR share a high active site residue similarity at the cofactor and substrate binding sites as well as a similar reaction mechanism with respect to the reductive half-reaction[5]. In Sec-mTrxRs, the 8 membered selenosulfide ring acts as an internal substrate that receives electrons from the N-terminal disulfide once it is reduced by NADPH. In contrast, GR and LipDP are essentially truncated forms of mTrxR that do not contain the flexible C-terminal tail. Instead, GR and LipDH reduce external substrates such as oxidized glutathione and lipoic acid, respectively[6].
   
   
== Mechanism ==
== Mechanism ==
Retrieved from "https://proteopedia.org/User:Emma_Ste.Marie/Sandbox_1"