{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T04:17:53Z","timestamp":1772770673643,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"vor","delay-in-days":1706,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2004,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Phosphorylation of phenylalanine hydroxylase (PAH) at Ser16 by cAMP\u2010dependent protein kinase increases the basal activity of the enzyme and its resistance to tryptic proteolysis. The modeled structures of the full\u2010length phosphorylated and unphosphorylated enzyme were subjected to molecular dynamics simulations, and we analyzed the energy of charge\u2013charge interactions for individual ionizable residues in the final structures. These calculations showed that the conformational changes induced by incorporation of phosphate were localized and limited mostly to the region around the phosphoserine (Arg13\u2013Asp17) and a region around the active site in the catalytic domain that includes residues involved in the binding of the iron and the substrate L\u2010Phe (Arg270 and His285). The absence of a generalized conformational change was confirmed by differential scanning calorimetry, thermal\u2010dependent circular dichroism, fluorescence spectroscopy, and limited chymotryptic proteolysis of the phosphorylated and unphosphorylated PAH. Our results explain the effect of phosphorylation of PAH on both the resistance to proteolysis specifically by trypsin\u2010like enzymes and on the increase in catalytic efficiency.<\/jats:p>","DOI":"10.1110\/ps.03595904","type":"journal-article","created":{"date-parts":[[2004,4,20]],"date-time":"2004-04-20T00:05:56Z","timestamp":1082419556000},"page":"1219-1226","source":"Crossref","is-referenced-by-count":24,"title":["Structural and stability effects of phosphorylation: Localized structural changes in phenylalanine hydroxylase"],"prefix":"10.1002","volume":"13","author":[{"given":"Frederico Faria","family":"Miranda","sequence":"first","affiliation":[]},{"given":"Matth\u00edas","family":"Th\u00f3r\u00f3lfsson","sequence":"additional","affiliation":[]},{"given":"Knut","family":"Teigen","sequence":"additional","affiliation":[]},{"given":"Jose 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