title: Structure of oncomodulin refined at 1.85 A resolution. An example of extensive molecular aggregation via Ca2+.
abstract: The crystal structure of oncomodulin, a 12,000 Mr protein isolated from rat tumours, has been determined by molecular replacement using the carp parvalbumin structure as a starting model. Refinement was performed by cycles of molecular fitting and restrained least-squares, using area-detector intensity data to 1.85 A resolution. For the 5770 reflections in the range 6.0 to 1.85 A, which were used in the refinement, the crystallographic R-factor is 0.166. The refined model includes residues 2 to 108, three Ca2+ and 87 water molecules per oncomodulin molecule. The oncomodulin backbone is closely related to that of parvalbumin; however, some differences are found after a least-squares fit of the two backbones, with root-mean-square (r.m.s.) deviations of 1 to 2 A in residues 2 to 6, 59 to 61 of the CD loop, 87, 90 and 108. The overall r.m.s. deviation of the backbone residues 5 to 108 is 0.62 A. Each of the two Ca2+ atoms that are bound to the CD and EF loops is co-ordinated to seven oxygen atoms, including one water molecule. The third Ca2+ is also seven-co-ordinated, to five oxygen atoms belonging to three different oncomodulin molecules and to two water molecules which form hydrogen bonds to a fourth oncomodulin; thus, this intermolecular Ca2+ and its equivalents interlink the molecules into zigzag layers normal to the b axis with a spacing of b/2 or 32.14 A. No such extensive molecular aggregation has been reported for any of the related Ca-binding regulatory proteins of the troponin-C family studied thus far. The Ca-O distances in all three polyhedra are in the range 2.07 A to 2.64 A, indicating tightly bound Ca polyhedra.
authors.affiliation: Division of Biological Sciences, National Research Council of Canada, Ottawa.
authors.forename: F R
authors.initials: FR
authors.lastname: Ahmed
authors.forename: M
authors.initials: M
authors.lastname: Przybylska
authors.forename: D R
authors.initials: DR
authors.lastname: Rose
authors.forename: G I
authors.initials: GI
authors.lastname: Birnbaum
authors.forename: M E
authors.initials: ME
authors.lastname: Pippy
authors.forename: J P
authors.initials: JP
authors.lastname: MacManus
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003196:Computer Graphics; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D010320:Parvalbumins / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D014961:X-Ray Diffraction
chemical_list: D002135:Calcium-Binding Proteins; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D010320:Parvalbumins; C034733:oncomodulin; D002118:Calcium