title: Structure of RC1339/APRc from Rickettsia conorii, a retropepsin-like aspartic protease.
abstract: The crystal structures of two constructs of RC1339/APRc from Rickettsia conorii, consisting of either residues 105-231 or 110-231 followed by a His tag, have been determined in three different crystal forms. As predicted, the fold of a monomer of APRc resembles one-half of the mandatory homodimer of retroviral pepsin-like aspartic proteases (retropepsins), but the quaternary structure of the dimer of APRc differs from that of the canonical retropepsins. The observed dimer is most likely an artifact of the expression and/or crystallization conditions since it cannot support the previously reported enzymatic activity of this bacterial aspartic protease. However, the fold of the core of each monomer is very closely related to the fold of retropepsins from a variety of retroviruses and to a single domain of pepsin-like eukaryotic enzymes, and may represent a putative common ancestor of monomeric and dimeric aspartic proteases.
authors.affiliation: Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Mi
authors.initials: M
authors.lastname: Li
authors.affiliation: Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Alla
authors.initials: A
authors.lastname: Gustchina
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Cruz
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Marisa
authors.initials: M
authors.lastname: Simões
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Curto
authors.affiliation: Vector-Borne Diseases Laboratories, Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Martinez
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Faro
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Isaura
authors.initials: I
authors.lastname: Simões
authors.affiliation: Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wlodawer
mesh_terms: D057055:Aspartic Acid Proteases / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D010434:Pepsin A / Q000737:chemistry*; D011487:Protein Conformation; D055503:Protein Multimerization; D020114:Rickettsia conorii / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D057055:Aspartic Acid Proteases; D010434:Pepsin A
keywords: aspartic proteases; bacterial proteases; dimeric proteins; enzyme evolution