title: Structural Insights into Substrate Binding of Brown Spider Venom Class II Phospholipases D.
abstract: Phospholipases D (PLDs), the major dermonecrotic factors from brown spider venoms, trigger a range of biological reactions both in vitro and in vivo. Despite their clinical relevance in loxoscelism, structural data is restricted to the apo-form of these enzymes, which has been instrumental in understanding the functional differences between the class I and II spider PLDs. The crystal structures of the native class II PLD from Loxosceles intermedia complexed with myo-inositol 1-phosphate and the inactive mutant H12A complexed with fatty acids indicate the existence of a strong ligand-dependent conformation change of the highly conserved aromatic residues, Tyr 223 and Trp225 indicating their roles in substrate binding. These results provided insights into the structural determinants for substrate recognition and binding by class II PLDs.
authors.forename: M A
authors.initials: MA
authors.lastname: Coronado
authors.forename: A
authors.initials: A
authors.lastname: Ullah
authors.forename: L S
authors.initials: LS
authors.lastname: da Silva
authors.forename: D
authors.initials: D
authors.lastname: Chaves-Moreira
authors.forename: L
authors.initials: L
authors.lastname: Vuitika
authors.forename: O M
authors.initials: OM
authors.lastname: Chaim
authors.forename: S S
authors.initials: SS
authors.lastname: Veiga
authors.forename: J
authors.initials: J
authors.lastname: Chahine
authors.forename: M T
authors.initials: MT
authors.lastname: Murakami
authors.affiliation: Centro Multiusuario de Inovacao Biomolecular, Departamento de Fisica, Universidade Estadual Paulista (UNESP), Sao Jose do Rio Preto, 15054-000 SP, Brazil. arni@sjrp.unesp.br.
authors.forename: R K
authors.initials: RK
authors.lastname: Arni
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002210:Caprylates / Q000378:metabolism; D018360:Crystallography, X-Ray; D007295:Inositol Phosphates; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010739:Phospholipase D / Q000737:chemistry* / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D013111:Spider Venoms / Q000737:chemistry* / Q000378:metabolism*; D013112:Spiders / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D002210:Caprylates; D007295:Inositol Phosphates; D050505:Mutant Proteins; D013111:Spider Venoms; C055161:loxosceles venom; C002647:inositol 1-phosphate; D010727:Phosphoric Diester Hydrolases; D010739:Phospholipase D; C031492:octanoic acid