RESUMO
Engineering functional protein scaffolds capable of carrying out chemical catalysis is a major challenge in enzyme design. Starting from a noncatalytic protein scaffold, we recently generated a new RNA ligase by in vitro directed evolution. This artificial enzyme lost its original fold and adopted an entirely new structure with substantially enhanced conformational dynamics, demonstrating that a primordial fold with suitable flexibility is sufficient to carry out enzymatic function.
Assuntos
Catálise , Engenharia de Proteínas/métodos , RNA Ligase (ATP)/química , Alanina/química , Sequência de Aminoácidos , Domínio Catalítico , Evolução Molecular Direcionada/métodos , Enzimas/química , Humanos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Metais/química , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Conformação Proteica , Dobramento de ProteínaRESUMO
Cancer treatments are often more successful when the disease is detected early. We evaluated the feasibility and safety of multicancer blood testing coupled with positron emission tomography-computed tomography (PET-CT) imaging to detect cancer in a prospective, interventional study of 10,006 women not previously known to have cancer. Positive blood tests were independently confirmed by a diagnostic PET-CT, which also localized the cancer. Twenty-six cancers were detected by blood testing. Of these, 15 underwent PET-CT imaging and nine (60%) were surgically excised. Twenty-four additional cancers were detected by standard-of-care screening and 46 by neither approach. One percent of participants underwent PET-CT imaging based on false-positive blood tests, and 0.22% underwent a futile invasive diagnostic procedure. These data demonstrate that multicancer blood testing combined with PET-CT can be safely incorporated into routine clinical care, in some cases leading to surgery with intent to cure.