Figure 4.
Figure 4 Active-site conformation of the autoinhibited forms
of titin kinase, twitchin and IRK. a, The active site of titin
kinase. The guanidinium group of R129 forms short hydrogen bonds
with the side chains of D127 and Y170 from the P+ 1 loop. There
is a weak direct hydrogen bond between D127 and Y170 (3.1 ring
in length). D127 forms further hydrogen bonds with Q150. b,
Twitchin active site^10. The catalytic aspartate, D174 forms
hydrogen bonds with K176, Q200 and R355 from the regulatory
tail. At the position of Y170 in titin kinase, there is an
alanine in twitchin. In the autoinhibited twitchin structure^10,
the catalytic aspartate is blocked by a salt bridge with an
arginine (R355 in twitchin) of the regulatory tail, suggesting a
different activation mechanism than for titin kinase. In titin
kinase, the equivalent arginine, R306, does not interact with
the catalytic aspartate. c, Active site of the autoinhibited
form of IRK17. The catalytic aspartate, D1132, is bound to
Y1162. This bond is disrupted after phosphorylation of Y1162,
accompanied by phosphorylation of two other tyrosines and
induces a conformational change of the activation segment from a
closed to an open conformation25. The colour codes of the tubes
are as in Fig. 3a. d, Stereo view of a 2F[o] - F[c]
electron-density map, using phases of the final model, contoured
at 1.3 .
The electron density shown covers several active-site residues
and solvent molecules. Some titin-kinase residues are labelled.
a-c were prepared with GRASP45 and d with program O (ref. 46).
The above figure is reprinted
by permission from Macmillan Publishers Ltd:
Nature
(1998,
395,
863-869)
copyright 1998.
ring
in length). D127 forms further hydrogen bonds with Q150. b,
Twitchin active site^10. The catalytic aspartate, D174 forms
hydrogen bonds with K176, Q200 and R355 from the regulatory
tail. At the position of Y170 in titin kinase, there is an
alanine in twitchin. In the autoinhibited twitchin structure^10,
the catalytic aspartate is blocked by a salt bridge with an
arginine (R355 in twitchin) of the regulatory tail, suggesting a
different activation mechanism than for titin kinase. In titin
kinase, the equivalent arginine, R306, does not interact with
the catalytic aspartate. c, Active site of the autoinhibited
form of IRK17. The catalytic aspartate, D1132, is bound to
Y1162. This bond is disrupted after phosphorylation of Y1162,
accompanied by phosphorylation of two other tyrosines and
induces a conformational change of the activation segment from a
closed to an open conformation25. The colour codes of the tubes
are as in Fig. 3a. d, Stereo view of a 2F[o] - F[c]
electron-density map, using phases of the final model, contoured
at 1.3 
.
The electron density shown covers several active-site residues
and solvent molecules. Some titin-kinase residues are labelled.
a-c were prepared with GRASP45 and d with program O (ref. 46).