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The structure reveals a weakly associated, activation\u2010loop swapped dimer with more than 20 amino acids of ordered density at the carboxy\u2010terminus. This C\u2010terminal PEST region binds intermolecularly to the hydrophobic groove of the N\u2010terminal domain of a neighboring molecule. Although the GLK activation loop mutant crystallized demonstrates reduced kinase activity, its structure demonstrates all the hallmarks of an \u201cactive\u201d kinase, including the salt bridge between the C\u2010helix glutamate and the catalytic lysine. Our compound displacement data suggests that the effect of the Ser170Ala mutation in reducing kinase activity is likely due to its effect in reducing substrate peptide binding affinity rather than reducing ATP binding or ATP turnover. This report details the first structure of GLK; comparison of its activation loop sequence and P\u2010loop structure to that of Map4k4 suggests ideas for designing inhibitors that can distinguish between these family members to achieve selective pharmacological inhibitors.<\/jats:p>","DOI":"10.1002\/pro.3062","type":"journal-article","created":{"date-parts":[[2016,10,13]],"date-time":"2016-10-13T16:29:21Z","timestamp":1476376161000},"page":"152-162","source":"Crossref","is-referenced-by-count":24,"title":["Germinal\u2010center kinase\u2010like kinase co\u2010crystal structure reveals a swapped activation loop and C\u2010terminal extension"],"prefix":"10.1002","volume":"26","author":[{"given":"Douglas","family":"Marcotte","sequence":"first","affiliation":[{"name":"Department of Drug Discovery Biogen Inc. 115 Binney Street Cambridge MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Rushe","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery Biogen Inc. 115 Binney Street Cambridge MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"M. 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