Summary: SelR domain
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Methionine sulfoxide reduction is an important process, by which cells regulate biological processes and cope with oxidative stress. MsrA, a protein involved in the reduction of methionine sulfoxides in proteins, has been known for four decades and has been extensively characterised with respect to structure and function. However, recent studies revealed that MsrA is only specific for methionine-S-sulfoxides. Because oxidised methionines occur in a mixture of R and S isomers in vivo, it was unclear how stereo-specific MsrA could be responsible for the reduction of all protein methionine sulfoxides. It appears that a second methionine sulfoxide reductase, SelR , evolved that is specific for methionine-R-sulfoxides, the activity that is different but complementary to that of MsrA. Thus, these proteins, working together, could reduce both stereoisomers of methionine sulfoxide. This domain is found both in SelR proteins and fused with the peptide methionine sulfoxide reductase enzymatic domain PF01625. The domain has two conserved cysteine and histidines. The domain binds both selenium and zinc . The final cysteine is found to be replaced by the rare amino acid selenocysteine in some members of the family . This family has methionine-R-sulfoxide reductase activity .
Lescure A, Gautheret D, Carbon P, Krol A; , J Biol Chem 1999;274:38147-38154.: Novel selenoproteins identified in silico and in vivo by using a conserved RNA structural motif. PUBMED:10608886 EPMC:10608886
Kryukov GV, Kumar RA, Koc A, Sun Z, Gladyshev VN; , Proc Natl Acad Sci U S A 2002;99:4245-4250.: Selenoprotein R is a zinc-containing stereo-specific methionine sulfoxide reductase. PUBMED:11929995 EPMC:11929995
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR002579
Peptide methionine sulphoxide reductase (Msr) reverses the inactivation of many proteins due to the oxidation of critical methionine residues by reducing methionine sulphoxide, Met(O), to methionine [PUBMED:10841552]. It is present in most living organisms, and the cognate structural gene belongs to the so-called minimum gene set [PUBMED:8994848, PUBMED:8816789].
The domains: MsrA and MsrB, reduce different epimeric forms of methionine sulphoxide. This group represents MsrB, the crystal structure of which has been determined to 1.8A [PUBMED:11938352]. The overall structure shows no resemblance to the structures of MsrA (INTERPRO) from other organisms; though the active sites show approximate mirror symmetry. In each case, conserved amino acid motifs mediate the stereo-specific recognition and reduction of the substrate. Unlike the MsrA domain, the MsrB domain activates the cysteine or selenocysteine nucleophile through a unique Cys-Arg-Asp/Glu catalytic triad. The collapse of the reaction intermediate most likely results in the formation of a sulphenic or selenenic acid moiety. Regeneration of the active site occurs through a series of thiol-disulphide exchange steps involving another active site Cys residue and thioredoxin.
In a number of pathogenic bacteria, including Neisseria gonorrhoeae, the MsrA and MsrB domains are fused; the MsrA being N-terminal to MsrB. This arrangement is reversed in Treponema pallidum. In N. gonorrhoeae and Neisseria meningitidis, a thioredoxin domain is fused to the N terminus. This may function to reduce the active sites of the downstream MsrA and MsrB domains.
|Molecular function||peptide-methionine-(S)-S-oxide reductase activity (GO:0008113)|
|Biological process||oxidation-reduction process (GO:0055114)|
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Curation and family details
|Seed source:||Pfam-B_1539 (release 4.1)|
|Author:||Bateman A, Enwright A|
|Number in seed:||18|
|Number in full:||5387|
|Average length of the domain:||121.70 aa|
|Average identity of full alignment:||48 %|
|Average coverage of the sequence by the domain:||59.33 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||13|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the SelR domain has been found. There are 31 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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