hysteretic behavior of proprotein convertase 13 (pc13)proprotein滞回行为的转化酶13(pc13).pdfVIP

Hysteretic Behavior of Proprotein Convertase 1/3 (PC1/3) 1 2 1 1 1 Marcelo Y. Icimoto , Nilana M. Barros , Juliana C. Ferreira , Marcelo F. Marcondes , Douglas Andrade , 1 1 ´ 3 1 1 Mauricio F. Machado , Maria A. Juliano , Wagner A. Judice , Luiz Juliano , Vitor Oliveira * ´ ˜ ˜ ˆ ˜ ˜ 1 Departamento de Biofısica, Universidade Federal de Sao Paulo, Sao Paulo, Brazil, 2 Ciencias Exatas e da Terra, Universidade Federal de Sao Paulo, Sao Paulo, Brazil, ˜ ´ ˜ 3 Centro Interdisciplinar de Investigac¸ao Bioquımica, Universidade de Mogi das Cruzes, Sao Paulo, Brazil Abstract The proprotein convertases (PCs) are calcium-dependent proteases responsible for processing precursor proteins into their active forms in eukariotes. The PC1/3 is a pivotal enzyme of this family that participates in the proteolytic maturation of prohormones and neuropeptides inside the regulated secretory pathway. In this paper we demonstrate that mouse proprotein convertase 1/3 (mPC1/3) has a lag phase of activation by substrates that can be interpreted as a hysteretic behavior of the enzyme for their hydrolysis. This is an unprecedented observation in peptidases, but is frequent in regulatory enzymes with physiological relevance. The lag phase of mPC1/3 is dependent on substrate, calcium