Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii
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MJ1511 was identified as an ORF in the M. jannaschii genome sequence. No function was assigned.
"A total of 1738 predicted protein-coding genes were identified; however, only a minority of these (38 percent) could be assigned a putative cellular role with high confidence"
The crystal structure of Mycobacterium tuberculosis alkylhydroperoxidase AhpD, a potential target for antitubercular drug design
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M. tuberculosis AhpD has a CXXC catalytic motif (Cys-130, Cys-133) essential for alkylhydroperoxidase activity. The structure reveals an all-helical fold.
"The two catalytic sulfhydryl groups, Cys-130 and Cys-133, are located near a central cavity in the trimer"
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The catalytic mechanism involves deprotonation of Cys-133 via a proton relay and subsequent disulfide bond formation.
"The structure supports a mechanism for the alkylhydroperoxidase activity in which Cys-133 is deprotonated by a distant glutamic acid via the relay action of His-137 and a water molecule"
The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics
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Mutagenesis confirms the CXXC-dependent catalytic mechanism of AhpD, with both catalytic cysteines essential for activity.
"The collective results strongly support the proposed catalytic mechanism for AhpD"
Crystal structure of alkyl hydroperoxidase D like protein PA0269 from Pseudomonas aeruginosa: homology of the AhpD-like structural family.
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P. aeruginosa AhpD-like protein has the same conserved CXXC motif and proton relay system as M. tuberculosis AhpD, with weak peroxidase activity.
"the functional activity is supplied by a proton relay system of five residues, Glu36, Cys48, Tyr50, Cys51, and His55, and one structural water molecule"
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The conserved catalytic CXXC sequence is present across functional members of the AhpD-like family.
"A comparison of five other related hypothetical proteins from various species, assigned to the alkyl hydroperoxidase D-like protein family, shows they contain the same conserved structural motif and catalytic sequence Cys-X-X-Cys"
Structure of lpg0406, a carboxymuconolactone decarboxylase family protein possibly involved in antioxidative response from Legionella pneumophila
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CMD family proteins share the AhpD-like fold and can have CXXC-dependent redox activity, but substrate preferences vary across family members.
"The protein has an all-helical fold with a conserved thioredoxin-like active site CXXC motif and a proton relay system similar to that of alkylhydroperoxidase from Mycobacterium tuberculosis"
Structure-function analyses of alkylhydroperoxidase D from Streptococcus pneumoniae reveal an unusual three-cysteine active site architecture
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Not all AhpD family members function as classical peroxidases. S. pneumoniae AhpD does not transfer electrons to AhpC and may instead act as a redox switch.
"We propose that it is unlikely that SpAhpD removes peroxides either directly or via AhpC, and that SpAhpD cysteine oxidation may act as a redox switch or mediate electron transfer with other thiol proteins"
Annotation inferences using phylogenetic trees
BioReason SFT trace for MJ1511 from HuggingFace protein catalogue
OpenScientist hypothesis run: MJ1511 pseudoenzyme / CXXC-loss (oxidoreductase over-annotation)
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Compute-driven (AlphaFold + Foldseek) structural analysis concludes the GO:0016491 oxidoreductase annotation is over-annotated and should be removed; MJ1511 lacks the CXXC motif and any histidine (Cys17/Cys107 are 36.52 Angstroms apart), and the paralog MJ0742 carries the same erroneous annotation, indicating a systematic mis-annotation of methanogen CMD proteins.
"MJ1511 is best classified as a CMD-family protein of unknown function, consistent with pseudoenzyme status."