title: The crystal structure of an intermediate dimer of aspergilloglutamic peptidase that mimics the enzyme-activation product complex produced upon autoproteolysis.
abstract: Aspergilloglutamic peptidase from Aspergillus niger var. macrosporus (AGP) is one of the so-called pepstatin-insensitive acid endopeptidases, which are distinct from the well-studied aspartic peptidases. Among the known homologues of the glutamic peptidases, AGP is a unique two-chain enzyme with a light chain and a heavy chain bound non-covalently with each other, and thus is an interesting target for protein structure-function relationship studies. In this article, we report the crystal structure of a dimeric form of the enzyme at a resolution of 1.6 Å. This form has a unique structure in which the C-terminal region of the light chain of one of the molecules binds to the active site cleft of the other molecule like a part of a substrate. This form mimics the enzyme-activation product complex produced upon autoproteolysis, and provides a structural clue that could help to clarify the activation mechanism. This type of dimeric structure of a peptidase is here reported for the first time.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Kubota
authors.forename: Woo C
authors.initials: WC
authors.lastname: Lee
authors.forename: Jun
authors.initials: J
authors.lastname: Ohtsuka
authors.forename: Masaki
authors.initials: M
authors.lastname: Kojima
authors.forename: So
authors.initials: S
authors.lastname: Iwata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakagawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Masaru
authors.initials: M
authors.lastname: Tanokura
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D001234:Aspergillus niger / Q000201:enzymology* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D019281:Dimerization; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D005656:Fungal Proteins; D009097:Multienzyme Complexes; D016282:Aspartic Acid Endopeptidases; C022442:aspergillopepsin II