Per citar aquest document: http://ddd.uab.cat/record/141717
Structural Characterization of the Enzymes Composing the Arginine Deiminase Pathway in Mycoplasma penetrans
Gallego Alonso, Pablo (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Planell Cerezo, Raquel (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Benach, Jordi (ALBA Synchrotron Light Source)
Querol Murillo, Enrique (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Pérez-Pons, Josep A. (Josep Antoni) (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Reverter i Cendrós, David (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Data: 2012
Resum: The metabolism of arginine towards ATP synthesis has been considered a major source of energy for microorganisms such as Mycoplasma penetrans in anaerobic conditions. Additionally, this pathway has also been implicated in pathogenic and virulence mechanism of certain microorganisms, i. e. protection from acidic stress during infection. In this work we present the crystal structures of the three enzymes composing the gene cluster of the arginine deiminase pathway from M. penetrans: arginine deiminase (ADI), ornithine carbamoyltransferase (OTC) and carbamate kinase (CK). The arginine deiminase (ADI) structure has been refined to 2. 3 Å resolution in its apo-form, displaying an “open” conformation of the active site of the enzyme in comparison to previous complex structures with substrate intermediates. The active site pocket of ADI is empty, with some of the catalytic and binding residues far from their active positions, suggesting major conformational changes upon substrate binding. Ornithine carbamoyltransferase (OTC) has been refined in two crystal forms at 2. 5 Å and 2. 6 Å resolution, respectively, both displaying an identical dodecameric structure with a 23-point symmetry. The dodecameric structure of OTC represents the highest level of organization in this protein family and in M. penetrans it is constituted by a novel interface between the four catalytic homotrimers. Carbamate kinase (CK) has been refined to 2. 5 Å resolution and its structure is characterized by the presence of two ion sulfates in the active site, one in the carbamoyl phosphate binding site and the other in the β-phosphate ADP binding pocket of the enzyme. The CK structure also shows variations in some of the elements that regulate the catalytic activity of the enzyme. The relatively low number of metabolic pathways and the relevance in human pathogenesis of Mycoplasma penetrans places the arginine deiminase pathway enzymes as potential targets to design specific inhibitors against this human parasite.
Nota: Número d'acord de subvenció EC/FP6/200346
Nota: Número d'acord de subvenció MICINN/BIO2007-67904-C02-01
Nota: Número d'acord de subvenció MICINN/BFU2008-0364
Nota: Número d'acord de subvenció MICINN/BFU2010- 22209-C02-01
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: article ; recerca ; publishedVersion
Matèria: Mycoplasma ; Arginine ; Enzyme structure ; Crystal structure ; Fungal structure ; Sulfates ; Sequence alignment ; Phosphates
Publicat a: PLoS one, Vol. 7 Issue 10 (October 2012) , p. e47886, ISSN 1932-6203

DOI: 10.1371/journal.pone.0047886


12 p, 764.1 KB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats

 Registre creat el 2015-10-19, darrera modificació el 2016-11-29



   Favorit i Compartir