As estimated, two billion people have been infected with HBV

mation. The rare helical conformation of aT is stabilized by the hydrophilic and hydrophobic interactions within the activation segment and with the surrounding secondary structure elements including helices aEF and aG and the aEFaF loop. Specifically, the hydroxyl of Thr177 forms hydrogenbonding interactions indirectly with the hydroxyl of Tyr195 and the main-chain carbonyl of Met168 via a water molecule, and the hydroxyl of Ser173 forms a hydrogen bond with the main-chain carbonyl of Lys167. In addition, Pro182 of the activation segment C-terminal to helix aT forms hydrophobic interactions with Leu190 of helix aEF and Leu226, Phe227, and Ile230 of helix aG, further Structure determination and refinement The structure of the CaMKI293-ATP complex was solved with the molecular replacement method implemented in program CNS using the apo rat CaMKI320 structure as the search model. The other structures of CaMKI were solved with the molecular replacement method using the structure of the CaMKI293-ATP complex as the search model. The model building was performed using Coot, and the structure refinement using programs CNS and REFMAC5. The statistics of the structure refinement and the structure models are also summarized in 2 Structures of Human CaMKIa apo CaMKI320 Data collection Space group a b c a, b, c Resolution C2 91.1 67.7 56.1 90, 99.8, 90 50.0-2.60 Rmerge ,I/sI). On the other hand, helix aT also forms a part of the interface of two two-fold symmetry-related molecules, and we performed crystal packing analysis to examine whether the conformation of helix aT is constrained by the crystal lattice. In the apo CaMKI320 belonging to space group C2, two-symmetry related molecules are juxtaposed head to tail, and the interface is formed mainly between helix aT of one molecule and helices aG and aEF of the other. The interface is stabilized mainly by hydrophobic interactions. Particularly, the side chains of Pro171, Leu175, and Cys179 of helix aT of one molecule make hydrophobic contacts with the side chains of Phe227 of helix aG and Leu190 of helix aEF of the other, forming a hydrophobic cluster. Interestingly, the unique conformation of helixaT captured in the apo CaMKI320 is also observed in the structure of CaMKI293 in complex with an inhibitor which is crystallized in a different space group, and in that structure the interface is formed by Relebactam chemical information similar structure elements of two twofold symmetry-related molecules but involves different interacting residues. In addition, in the CaMKI320-ATP and CaMKI315-ATP structures which are crystallized in another space group, two pseudo two-fold symmetry-related molecules are juxtaposed head to tail in a similar way as in the apo CaMKI320. Consistently, the interface is comparable to that in the apo CaMKI320 and particularly, helices aG and aEF occupy similar positions as those in the apo CaMKI320 structure. However, helix aT is largely disordered in one molecule and completely disordered in the other, although the hydrophobic cluster at the interface is partially maintained. In contrast, in the CaMKI293-ATP structure which is crystallized in space group I222, the C-terminal part of the activation segment is completely disordered, and the two symmetry-related molecules are juxtaposed head to head. Correspondingly, the interface is substantially different from those in the CaMKI320, CaMKI320ATP, and CaMKI315-ATP structures. Taken together, these results indicate that the activation segment has a high flexib