confirmed. Although a certain degree of specificity was claimed in the corresponding
publications, it is likely that the highly reactive α,β-unsaturated ketones representing
the active species covalently modify additional targets beyond JAK3.
Fig. 4 Alignment of the amino acids contributing to the Janus kinases’ ATP pockets and
the adjacent regions (generated by superposition from the JAK3 X-ray crystal structure with the
PDB-code 3LXK). Colors/roman numbers were assigned according to the kinases’ subdomain
structure proposed by Hanks and Hunter [36]. The sequence and numbering of JAK3 is used as
basis for the alignment, and differing amino acids in other JAKs are highlighted in darker colors.
Amino acids contributing to the binding pocket only via their backbone are further marked with
an asterisk. Cys909 and Ala966 (highlighted with a black frame) are the key discriminators
between JAK3 and other JAK family members
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M. Gehringer and M. Forster
publications, it is likely that the highly reactive α,β-unsaturated ketones representing
the active species covalently modify additional targets beyond JAK3.
Fig. 4 Alignment of the amino acids contributing to the Janus kinases’ ATP pockets and
the adjacent regions (generated by superposition from the JAK3 X-ray crystal structure with the
PDB-code 3LXK). Colors/roman numbers were assigned according to the kinases’ subdomain
structure proposed by Hanks and Hunter [36]. The sequence and numbering of JAK3 is used as
basis for the alignment, and differing amino acids in other JAKs are highlighted in darker colors.
Amino acids contributing to the binding pocket only via their backbone are further marked with
an asterisk. Cys909 and Ala966 (highlighted with a black frame) are the key discriminators
between JAK3 and other JAK family members
232
M. Gehringer and M. Forster