It is well known that motion of LID and NMP-binding (NMPbind) domains in adenylate kinase (AK) is important in ligand binding and catalysis. However, the nature of such domain motions is poorly characterized. One of the Critical hinge regions is hinge IV, which connects the CORE and LID domains. In addition, the hinge IV contains a strictly conserved residue. L171, in the AK family. To investigate the role of hinge IV. crystal Structure Of human adenylate kinase 4 (AK4) L171 P Mutant was determined. This mutation dramatically changes the orientation of the LID domain, which could be described as a novel twisted- and-closed conformation in contrast to the open and closed conformations in other AKs. This mutant provides a new example of domain motions in AK family. (C) 2008 Elsevier Inc. All rights reserved.