RESUMEN
Unicuspid aortic valve is a rare congenital malformation that usually presents in the 3rd to 5th decade of life-and usually with severe aortic stenosis or regurgitation. It often requires surgical correction. Diagnosis can be made with 2- or 3-dimensional transthoracic or transesophageal echocardiography, cardiac computed tomography, or cardiac magnetic resonance imaging. We report the case of a 31-year-old man who presented with dyspnea on exertion due to severe aortic stenosis secondary to a unicuspid unicommissural aortic valve. After aortic valve replacement, this patient experienced complete heart block that required the placement of a permanent pacemaker.
Asunto(s)
Estenosis de la Válvula Aórtica/etiología , Válvula Aórtica/anomalías , Adulto , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Humanos , MasculinoRESUMEN
The Haemophilus influenzae beta-carbonic anhydrase (HICA) allosteric site variants V47A and G41A were overexpressed and purified to homogeneity. These variants have k(cat)/K(m) values similar to that of the wild-type enzyme and exhibit a similar dramatic decrease in catalytic activity at pH <8.0. However, both HICA-G41A and -V47A were serendipitously found to bind sulfate ion or bicarbonate ion near pairs of Glu50 and Arg64 residues located on the dimerization interface. In the case of HICA-V47A, bicarbonate ions simultaneously bind to both the dimerization interface and the allosteric sites. For HICA-G41A, two of 12 chains in the asymmetric unit bind bicarbonate ion exclusively at the dimerization interface, while the remaining 10 chains bind bicarbonate ion exclusively at the allosteric site. We propose that the new anion binding site along the dimerization interface of HICA is an "escort" site that represents an intermediate along the ingress and egress route of bicarbonate ion to and from the allosteric binding site, respectively. The structural evidence for sulfate binding at the escort site suggests that the mechanism of sulfate activation of HICA is the result of sulfate ion competing for bicarbonate at the escort site, preventing passage of bicarbonate from the bulk solution to its allosteric site.
Asunto(s)
Bicarbonatos/química , Anhidrasas Carbónicas/química , Anhidrasas Carbónicas/metabolismo , Haemophilus influenzae/enzimología , Sitio Alostérico , Sustitución de Aminoácidos , Bicarbonatos/metabolismo , Sitios de Unión , Anhidrasas Carbónicas/genética , Catálisis , Dominio Catalítico , Cristalografía por Rayos X , Dimerización , Cinética , Modelos Químicos , Modelos Moleculares , Estructura Molecular , Mutagénesis Sitio-Dirigida , Mutación/genética , Oxidación-Reducción , Conformación Proteica , Sulfatos/química , Sulfatos/metabolismoRESUMEN
Cripto-1, a co-receptor for Nodal, can activate Nodal-dependent and Nodal-independent signaling pathways. In this study we have investigated whether Cripto-1 mutants, that fail to activate a Nodal-dependent signaling pathway, are capable to activate a Nodal-independent signaling pathway in mammary epithelial cells. Cripto-1 mutants expressed in EpH4 mouse mammary epithelial cells are fully functional in regard to activation of a Nodal-independent signaling pathway, leading to phosphorylation of mitogen-activated protein kinase (MAPK) and Akt and to enhanced proliferation and motility of these cells, suggesting that Cripto-1 mutants with impaired Nodal signaling are still active in a Nodal-independent signaling pathway.