title: A Maltose-Binding Protein Fusion Construct Yields a Robust Crystallography Platform for MCL1.
abstract: Crystallization of a maltose-binding protein MCL1 fusion has yielded a robust crystallography platform that generated the first apo MCL1 crystal structure, as well as five ligand-bound structures. The ability to obtain fragment-bound structures advances structure-based drug design efforts that, despite considerable effort, had previously been intractable by crystallography. In the ligand-independent crystal form we identify inhibitor binding modes not observed in earlier crystallographic systems. This MBP-MCL1 construct dramatically improves the structural understanding of well-validated MCL1 ligands, and will likely catalyze the structure-based optimization of high affinity MCL1 inhibitors.
authors.affiliation: Beryllium, Bedford, Massachusetts, United States of America.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Clifton
authors.affiliation: Beryllium, Bedford, Massachusetts, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Dranow
authors.affiliation: The Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Alison
authors.initials: A
authors.lastname: Leed
authors.affiliation: The Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Ben
authors.initials: B
authors.lastname: Fulroth
authors.affiliation: Beryllium, Bedford, Massachusetts, United States of America.
authors.forename: James W
authors.initials: JW
authors.lastname: Fairman
authors.affiliation: Beryllium, Bedford, Massachusetts, United States of America.
authors.forename: Jan
authors.initials: J
authors.lastname: Abendroth
authors.affiliation: Beryllium, Bedford, Massachusetts, United States of America.
authors.forename: Kateri A
authors.initials: KA
authors.lastname: Atkins
authors.affiliation: Beryllium, Bedford, Massachusetts, United States of America.
authors.forename: Ellen
authors.initials: E
authors.lastname: Wallace
authors.affiliation: Acme Bioscience, Palo Alto, California, United States of America.
authors.forename: Dazhong
authors.initials: D
authors.lastname: Fan
authors.affiliation: Acme Bioscience, Palo Alto, California, United States of America.
authors.forename: Guoping
authors.initials: G
authors.lastname: Xu
authors.affiliation: Acme Bioscience, Palo Alto, California, United States of America.
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Ni
authors.affiliation: The Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Doug
authors.initials: D
authors.lastname: Daniels
authors.affiliation: Van Drie Research, North Andover, Massachusetts, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Van Drie
authors.affiliation: The Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Guo
authors.initials: G
authors.lastname: Wei
authors.affiliation: The Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Alex B
authors.initials: AB
authors.lastname: Burgin
authors.affiliation: The Broad Institute, Cambridge, Massachusetts, United States of America; Dana-Farber Cancer Institute and Howard Hughes Medical Institute, Boston, Massachusetts, United States of America.
authors.forename: Todd R
authors.initials: TR
authors.lastname: Golub
authors.affiliation: The Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Hubbard
authors.affiliation: The Broad Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Serrano-Wu
mesh_terms: D001059:Apoproteins / Q000737:chemistry / Q000235:genetics; D003460:Crystallization; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008024:Ligands; D058619:Maltose-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D011485:Protein Binding; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D001059:Apoproteins; D008024:Ligands; C579095:MCL1 protein, human; D058619:Maltose-Binding Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins