Pereira JH

References (2)

Title : Accurate prediction of protein structures and interactions using a three-track neural network - Baek_2021_Science_373_871
Author(s) : Baek M , DiMaio F , Anishchenko I , Dauparas J , Ovchinnikov S , Lee GR , Wang J , Cong Q , Kinch LN , Schaeffer RD , Millan C , Park H , Adams C , Glassman CR , DeGiovanni A , Pereira JH , Rodrigues AV , van Dijk AA , Ebrecht AC , Opperman DJ , Sagmeister T , Buhlheller C , Pavkov-Keller T , Rathinaswamy MK , Dalwadi U , Yip CK , Burke JE , Garcia KC , Grishin NV , Adams PD , Read RJ , Baker D
Ref : Science , 373 :871 , 2021
Abstract : DeepMind presented notably accurate predictions at the recent 14th Critical Assessment of Structure Prediction (CASP14) conference. We explored network architectures that incorporate related ideas and obtained the best performance with a three-track network in which information at the one-dimensional (1D) sequence level, the 2D distance map level, and the 3D coordinate level is successively transformed and integrated. The three-track network produces structure predictions with accuracies approaching those of DeepMind in CASP14, enables the rapid solution of challenging x-ray crystallography and cryo-electron microscopy structure modeling problems, and provides insights into the functions of proteins of currently unknown structure. The network also enables rapid generation of accurate protein-protein complex models from sequence information alone, short-circuiting traditional approaches that require modeling of individual subunits followed by docking. We make the method available to the scientific community to speed biological research.
ESTHER : Baek_2021_Science_373_871
PubMedSearch : Baek_2021_Science_373_871
PubMedID: 34282049

Title : Structure and Function of BorB, the Type II Thioesterase from the Borrelidin Biosynthetic Gene Cluster - Curran_2020_Biochemistry__
Author(s) : Curran SC , Pereira JH , Baluyot MJ , Lake J , Puetz H , Rosenburg DJ , Adams P , Keasling JD
Ref : Biochemistry , : , 2020
Abstract : alpha/beta hydrolases make up a large and diverse protein superfamily. In natural product biosynthesis, cis-acting thioesterase alpha/beta hydrolases can terminate biosynthetic assembly lines and release products by hydrolyzing or cyclizing the biosynthetic intermediate. Thioesterases can also act in trans, removing aberrant intermediates and restarting stalled biosynthesis. Knockout of this "editing" function leads to reduced product titers. The borrelidin biosynthetic gene cluster from Streptomyces parvulus Tu4055 contains a hitherto uncharacterized stand-alone thioesterase, borB. In this work, we demonstrate that purified BorB cleaves acyl substrates with a preference for propionate, which supports the hypothesis that it is also an editing thioesterase. The crystal structure of BorB shows a wedgelike hydrophobic substrate binding crevice that limits substrate length. To investigate the structure-function relationship, we made chimeric BorB variants using loop regions from characterized homologues with different specificities. BorB chimeras slightly reduced activity, arguing that the modified region is a not major determinant of substrate preference. The structure-function relationships described here contribute to the process of elimination for understanding thioesterase specificity and, ultimately, engineering and applying trans-acting thioesterases in biosynthetic assembly lines.
ESTHER : Curran_2020_Biochemistry__
PubMedSearch : Curran_2020_Biochemistry__
PubMedID: 32250597
Gene_locus related to this paper: 9acto-q70i09