ROMERO JORGE MIGUEL
Congresos y reuniones científicas
Título:
S-NITROSYLATION ON HUMAN TRIOSEPHOSHATE ISOMERASE: STRUCTURAL AND BIOCHEMICAL STUDIES
Autor/es:
ROMERO JM; CARRIZO, M E; CURTINO JA
Lugar:
Buenos Aires
Reunión:
Congreso; LIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN BIOQUÍMICA Y BIOLOGÍA MOLECULAR; 2017
Resumen:
Nitricoxide (NO) is a diatomic gaseous free radical produced in large amounts bymacrophages upon the induction of NO synthetase. One of the mayor consequencesof NO exposure is the generation of the protein S-nitrosylation, which could producealterations in protein function. Even though the S-nitrosylation mechanism in vivo is unclear, several reactivenitrogen species were proposed as mediators including NO gas, or non proteinS-nitrosothiols as S-nitrosocysteine (CySNO) and S-nitrosoglutathione (GSNO). Triosephosphateisomerase (TPI) has been frequently identified as a target S-nitrosylation byproteomic studies. TPI is a dimeric enzyme that catalyzes the isomerization ofdihydroxyacetone phosphate (DHAP) to glyceraldehydes-3-phosphate (G3P), and itis found in almost all organisms. However the effects of S-nitrosylation onactivity were only explored in plants and algae. Here, we present results abouton the S-nitrosylation of human TPI (hTPI), and the effect on its enzymaticparameters. hTPI is S-nitrosylated by S-transnitrosylation mechanism in atime-dependent manner by both, CySNO and GSNO, being CySNO more efficient.Both, x-ray crystal structure and mass spectrometry analysis showed that Cys217was S-nitrosylated just in one subunit of the dimer. hTPI S-nitrosylationproduced a 15% inhibition of the Vmax of the DHAP to G3P conversion. However, wedid not observe effect on the Km. This is the first in vitro study of the hTPI S-nitrosylation. Further studies will berequired to identify the structural basis of the inhibition