Sandbox Reserved 818: Difference between revisions

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labeled in blue: catalytic residues (His35, Glu129) <br />
labeled in blue: catalytic residues (His35, Glu129) <br />


The ADP-ribosylation of trimeric G proteins occurs on a '''cysteine residue''' in the ''C-terminal part of the α-subunit'' [88]. <br />
The ADP-ribosylation of trimeric G proteins occurs on a '''cysteine residue''' in the ''C-terminal part of the α-subunit''
For that, the donor substrate used by PTX is '''NAD<sup>+</sup>''', which binds the toxin through '''Trp26''' [93,94], '''Arg9''' [95] and '''Cys41''' [92] located in the ''active site of S1''. <br />
<ref name="Moss85">
Concerning the acceptor substrate, it binds to the toxin through '''residues 180-219''' in the ''C-terminal region of S1'' [91]. These residues show indeed a high affinity for the G protein and are involved in the catalysis of the ADP-ribosylation [97]. <br />
Hsia, J. A., Tsai, S. C., Adamik, R., Yost, D. A., Hewlett, E. L., & Moss, J. (1985). Amino acid-specific ADP-ribosylation. Sensitivity to hydroxylamine of [cysteine (ADP-ribose)] protein and [arginine (ADP-ribose)] protein linkages. Journal of Biological Chemistry, 260(30), 16187-16191.
In the S1 subunit, the ''catalytic residues'' '''His35''' [96,97] and '''Glu129''' [98] have been identified: His35 is involved in the ionization of the nucleophilic thiol of the cysteine residue in the G protein via its ε-N [99] and the carboxylate group of the Glu129 side chain is in contact with the 2'-ribo-hydroxyl of the NAD<sup>+</sup> [90].
</ref>. <br />
For that, the donor substrate used by PTX is '''NAD<sup>+</sup>''', which binds the toxin through '''Trp26'''  
<ref name="Barbieri89">
Cortina, G. & Barbieri, J. T. (1989). Role of tryptophan 26 in the NAD glycohydrolase reaction of the S-1 subunit of pertussis toxin. J. Biol. Chem. 264: 17322-17328.
</ref>
<ref name="Feron89">
Locht, C., Capiau, C., & Feron, C. (1989). Identification of amino acid residues essential for the enzymatic activities of pertussis toxin. Proceedings of the National Academy of Sciences, 86(9), 3075-3079.
</ref>
, '''Arg9'''  
<ref name="Keith88">
Burnette, W. N., Cieplak, W. I. T. O. L. D., Mar, V. L., Kaljot, K. T., Sato, H., & Keith, J. M. (1988). Pertussis toxin S1 mutant with reduced enzyme activity and a conserved protective epitope. Science, 242(4875), 72-74.
</ref>
and '''Cys41'''  
<ref name="Keith90">
Locht, C., Lobet, Y., Feron, C., Cieplak, W., & Keith, J. M. (1990). The role of cysteine 41 in the enzymatic activities of the pertussis toxin S1 subunit as investigated by site-directed mutagenesis. Journal of Biological Chemistry, 265(8), 4552-4559.
</ref>
located in the ''active site of S1''. <br />
Concerning the acceptor substrate, it binds to the toxin through '''residues 180-219''' in the ''C-terminal region of S1''  
<ref name="Barbieri91">
Cortina, G., Krueger, K. M., & Barbieri, J. T. (1991). The carboxyl terminus of the S1 subunit of pertussis toxin confers high affinity binding to transducin. Journal of Biological Chemistry, 266(35), 23810-23814.
</ref>.
These residues show indeed a high affinity for the G protein and are involved in the catalysis of the ADP-ribosylation  
<ref name="Barbieri94">
Xu, Y., Barbancon-Finck, V., & Barbieri, J. T. (1994). Role of histidine 35 of the S1 subunit of pertussis toxin in the ADP-ribosylation of transducin. Journal of Biological Chemistry, 269(13), 9993-9999.
</ref>. <br />
In the S1 subunit, the ''catalytic residues'' '''His35'''  
<ref name="Locht94">
Antoine, R., & Locht, C. (1994). The NAD-glycohydrolase activity of the pertussis toxin S1 subunit. Involvement of the catalytic HIS-35 residue. Journal of Biological Chemistry, 269(9), 6450-6457.
</ref>
<ref name="Barbieri94"></ref>
and '''Glu129'''  
<ref name="Locht93">
Antoine, R., Tallett, A., Van Heyningen, S., & Locht, C. (1993). Evidence for a catalytic role of glutamic acid 129 in the NAD-glycohydrolase activity of the pertussis toxin S1 subunit. Journal of Biological Chemistry, 268(32), 24149-24155.
</ref>
have been identified: His35 is involved in the ionization of the nucleophilic thiol of the cysteine residue in the G protein via its ε-N [99] and the carboxylate group of the Glu129 side chain is in contact with the 2'-ribo-hydroxyl of the NAD<sup>+</sup>  
<ref name="Antoine95">
Locht, C., & Antoine, R. (1995). A proposed mechanism of ADP-ribosylation catalyzed by the pertussis toxin S1 subunit. Biochimie, 77(5), 333-340.
</ref>.


==Toxic effects of pertussis toxin==
==Toxic effects of pertussis toxin==
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