RESUMO
Crotoxin B is a basic phospholipase A(2) found in the venom of several Crotalus durissus ssp. rattlesnakes and is one of the subunits that constitute crotoxin, the main component of the venom of these snakes. This heterodimeric toxin is related to important envenomation effects such as neurological disorders, myotoxicity and renal failure. Although crotoxin was first crystallized in 1938, the first structural data only became available in 2007 (for crotoxin B from C. durissus terrificus) and showed an ambiguous result for the biological assembly, which could be either dimeric or tetrameric. In this work, the crystallization, X-ray diffraction data collection at 2.2 A resolution and molecular-replacement solution of a dimeric complex formed by two crotoxin B isoforms from C. durissus collilineatus venom is presented.
Assuntos
Crotoxina/química , Animais , Venenos de Crotalídeos/química , Crotoxina/isolamento & purificação , Cristalização , Cristalografia por Raios X , Dimerização , Fosfolipases A2/química , Estrutura Quaternária de ProteínaAssuntos
Anticorpos Monoclonais/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome de Stevens-Johnson/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Infliximab , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Crotoxin B is a basic phospholipase A2 found in the venom of Crotalus durissus terrificus and is one of the subunits that constitute crotoxin. This heterodimeric toxin, which is the main component of C. d. terrificus venom, is completed by an acidic, nontoxic and non-enzymatic component (crotoxin A) and is involved in important envenomation effects, such as neurological disorders, myotoxicity and renal failure. Although crotoxin was first crystallized in 1938, no crystal structure is currently available for crotoxin, crotoxin A or crotoxin B. In this work, the crystallization, X-ray diffraction data collection to 2.28 A resolution and molecular-replacement solution of a novel tetrameric complex formed by two dimers of crotoxin B isoforms (CB1 and CB2) is presented.
Assuntos
Crotalus/metabolismo , Crotoxina/química , Crotoxina/metabolismo , Fosfolipases A2/química , Fosfolipases A2/metabolismo , Venenos de Serpentes/química , Venenos de Serpentes/metabolismo , Animais , Crotalus/genética , Crotoxina/genética , Cristalização , Isoenzimas/química , Isoenzimas/metabolismo , Modelos Moleculares , Fosfolipases A2/genética , Ligação Proteica , Estrutura Quaternária de Proteína , Venenos de Serpentes/genética , Difração de Raios XRESUMO
For the first time, a complete X-ray diffraction data set has been collected from a myotoxic Asp49-phospholipase A2 (Asp49-PLA2) with low catalytic activity (BthTX-II from Bothrops jararacussu venom) and a molecular-replacement solution has been obtained with a dimer in the asymmetric unit. The quaternary structure of BthTX-II resembles the myotoxin Asp49-PLA2 PrTX-III (piratoxin III from B. pirajai venom) and all non-catalytic and myotoxic dimeric Lys49-PLA2s. In contrast, the oligomeric structure of BthTX-II is different from the highly catalytic and non-myotoxic BthA-I (acidic PLA2 from B. jararacussu). Thus, comparison between these structures should add insight into the catalytic and myotoxic activities of bothropic PLA2s.
Assuntos
Asparagina , Bothrops , Venenos de Crotalídeos/toxicidade , Fosfolipases A/toxicidade , Animais , Catálise , Venenos de Crotalídeos/química , Venenos de Crotalídeos/metabolismo , Cristalografia por Raios X , Cinética , Fosfolipases A/química , Fosfolipases A/isolamento & purificação , Fosfolipases A/metabolismo , Fosfolipases A2 , Conformação ProteicaRESUMO
Paracoccidioidomycosis is an endemic South American systemic mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis (P. brasiliensis). The main clinical form of disease is pulmonary, but all organs may be involved. We report a case of overinfection by P. brasiliensis in chronic gouty arthritis affecting the proximal phalanx of the right hallux. The patient required proximal amputation and long-term antifungal therapy.