Home About us Contact | |||
Functional Flexibility (functional + flexibility)
Selected AbstractsStructural insight into the evolutionary and pharmacologic homology of glutamate carboxypeptidases II and IIIFEBS JOURNAL, Issue 16 2009Klara Hlouchova Glutamate carboxypeptidase III (GCPIII) is a metalloenzyme that belongs to the transferrin receptor/glutamate carboxypeptidase II (GCPII; EC 3.4.17.21) superfamily. GCPIII has been studied mainly because of its evolutionary relationship to GCPII, an enzyme involved in a variety of neuropathologies and malignancies, such as glutamatergic neurotoxicity and prostate cancer. Given the potential functional and pharmacological overlap between GCPIII and GCPII, studies addressing the structural and physiological properties of GCPIII are crucial for obtaining a deeper understanding of the GCPII/GCPIII system. In the present study, we report high-resolution crystal structures of the human GCPIII ectodomain in a ,pseudo-unliganded' state and in a complex with: (a) l -glutamate (a product of hydrolysis); (b) a phosphapeptide transition state mimetic, namely (2S,3,S)-{[(3,-amino-3,-carboxy-propyl)-hydroxyphosphinoyl]methyl}-pentanedioic acid; and (c) quisqualic acid, a glutamate biostere. Our data reveal the overall fold and quaternary arrangement of the GCPIII molecule, define the architecture of the GCPIII substrate-binding cavity, and offer an experimental evidence for the presence of Zn2+ ions in the bimetallic active site. Furthermore, the structures allow us to detail interactions between the enzyme and its ligands and to characterize the functional flexibility of GCPIII, which is essential for substrate recognition. A comparison of these GCPIII structures with the equivalent GCPII complexes reveals differences in the organization of specificity pockets, in surface charge distribution, and in the occupancy of the co-catalytic zinc sites. The data presented here provide information that should prove to be essential for the structurally-aided design of GCPIII-specific inhibitors and might comprise guidelines for future comparative GCPII/GCPIII studies. [source] Managing functional flexibility in a passenger transport firmHUMAN RESOURCE MANAGEMENT JOURNAL, Issue 4 2003Mandy van der Velde In this study we focus on how a Dutch passenger transport firm managed the functional flexibility of employees when it had to become more flexible due to increased competition. Specifically, we examine the relationships between the personal characteristics of employees and their work perceptions on the one hand and their functional flexibility on the other. Our results show that functional flexibility consists of two dimensions, willingness and ability to be flexible, and that work perceptions are more closely related to the willingness, rather than the ability, to be flexible. Willingness to be flexible was positively related to need for growth, tendency for innovation, organisational support and negatively to task formalisation. Ability to be flexible was related to need for growth, tendency for innovation and general self-efficacy. The implications for management are then discussed. [source] Reproducible growth of well diffracting ribosomal crystalsACTA CRYSTALLOGRAPHICA SECTION D, Issue 6 2005Tamar Auerbach-Nevo The crystallization of ribosomal particles is associated with extraordinary challenging demands. This originates mainly from the ribosome's natural tendency to deteriorate and from its multi-conformational heterogeneity, both of which stem from its functional flexibility. To increase the level of homogeneity of ribosomal preparations, systematic searches for conditions yielding populations of fully defined chemical compositions were employed and the variables essential for high functional activity were analyzed and optimized. These include temperature, cell-growth duration and media, the cell-harvesting stage, ribosomal purification and storage. The functional state that is most suitable to yield quality crystals was identified as that of the polysome and it was found that this fraction reproducibly yielded crystals of superior properties. [source] Organizing Flexibility: The Flexible Firm in a New CenturyBRITISH JOURNAL OF INDUSTRIAL RELATIONS, Issue 4 2001Arne L. Kalleberg Research on organizational flexibility should examine the linkages between numerical and functional flexibility. Unfortunately, studies of each type of flexibility generally neglect the other. Moreover, the most popular conception of the interplay between these two forms of flexibility , the core,periphery model , is incomplete in important ways. I discuss evidence and limitations of the core,periphery model of the flexible firm, and outline some promising attempts to conceptualize how organizations may combine functional and numerical flexibility. I focus mainly on the USA and the UK, though I also review evidence and issues involved in cross-national differences in organizational flexibility. [source] |