Common conformational changes in flavodoxins induced by FMN and anion binding: The structure of <I>Helicobacter pylori</I> apoflavodoxin Export

@article{citeulike:4087799, abstract = {Flavodoxins, noncovalent complexes between apoflavodoxins and flavin mononucleotide (FMN), are useful models to investigate the mechanism of protein/flavin recognition. In this respect, the only available crystal structure of an apoflavodoxin (that from Anabaena) showed a closed isoalloxazine pocket and the presence of a bound phosphate ion, which posed many questions on the recognition mechanism and on the potential physiological role exerted by phosphate ions. To address these issues we report here the X-ray structure of the apoflavodoxin from the pathogen Helicobacter pylori. The protein naturally lacks one of the conserved aromatic residues that close the isoalloxazine pocket in Anabaena, and the structure has been determined in a medium lacking phosphate. In spite of these significant differences, the isoallozaxine pocket in H. pylori apoflavodoxin appears also closed and a chloride ion is bound at a native-like FMN phosphate site. It seems thus that it is a general characteristic of apoflavodoxins to display closed, non-native, isoalloxazine binding sites together with native-like, rather promiscuous, phosphate binding sites that can bear other available small anions present in solution. In this respect, both binding energy hot spots of the apoflavodoxin/FMN complex are initially unavailable to FMN binding and the specific spot for FMN recognition may depend on the dynamics of the two candidate regions. Molecular dynamics simulations show that the isoalloxazine binding loops are intrinsically flexible at physiological temperatures, thus facilitating the intercalation of the cofactor, and that their mobility is modulated by the anion bound at the phosphate site. Proteins 2007. {\copyright} 2007 Wiley-Liss, Inc.}, address = {Biocomputation and Complex Systems Physics Institute (BiFi), Universidad de Zaragoza, Unidad Asociada al IQFR-CSIC; Departamento de Bioqu\'{\i}mica y Biolog\'{\i}a Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain; Grupo de Cristalograf\'{\i}a Molecular y Biolog\'{\i}a Estructural, Instituto Qu\'{\i}mica-F\'{\i}sica Rocasolano, Consejo Superior de Investigaciones Cient\'{\i}ficas, Serrano 119, 28006 Madrid, Spain; Departamento de F\'{\i}sica de la Materia Condensada, Facultad de Ciencias, Universidad de Zaragoza}, author = {Mart\'{\i}nez-J\'{u}lvez, Marta and Cremades, Nunilo and Bueno, Marta and P\'{e}rez-Dorado, Inmaculada and Maya, Celia and Cuesta-L\'{o}pez, Santiago and Prada-Gracia, Diego and Falo, Fernando and Hermoso, Juan A. and Sancho, Javier}, citeulike-article-id = {4087799}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/prot.21410}, citeulike-linkout-1 = {http://www3.interscience.wiley.com/cgi-bin/abstract/114290976/ABSTRACT}, doi = {10.1002/prot.21410}, journal = {Proteins: Structure, Function, and Bioinformatics}, keywords = {mios}, number = {3}, pages = {581--594}, posted-at = {2009-02-23 21:07:57}, priority = {2}, title = {Common conformational changes in flavodoxins induced by FMN and anion binding: The structure of <I>Helicobacter pylori</I> apoflavodoxin}, url = {http://dx.doi.org/10.1002/prot.21410}, volume = {69}, year = {2007} }

TY - JOUR ID - citeulike:4087799 L3 - citeulike-article-id:4087799 N2 - Flavodoxins, noncovalent complexes between apoflavodoxins and flavin mononucleotide (FMN), are useful models to investigate the mechanism of protein/flavin recognition. In this respect, the only available crystal structure of an apoflavodoxin (that from Anabaena) showed a closed isoalloxazine pocket and the presence of a bound phosphate ion, which posed many questions on the recognition mechanism and on the potential physiological role exerted by phosphate ions. To address these issues we report here the X-ray structure of the apoflavodoxin from the pathogen Helicobacter pylori. The protein naturally lacks one of the conserved aromatic residues that close the isoalloxazine pocket in Anabaena, and the structure has been determined in a medium lacking phosphate. In spite of these significant differences, the isoallozaxine pocket in H. pylori apoflavodoxin appears also closed and a chloride ion is bound at a native-like FMN phosphate site. It seems thus that it is a general characteristic of apoflavodoxins to display closed, non-native, isoalloxazine binding sites together with native-like, rather promiscuous, phosphate binding sites that can bear other available small anions present in solution. In this respect, both binding energy hot spots of the apoflavodoxin/FMN complex are initially unavailable to FMN binding and the specific spot for FMN recognition may depend on the dynamics of the two candidate regions. Molecular dynamics simulations show that the isoalloxazine binding loops are intrinsically flexible at physiological temperatures, thus facilitating the intercalation of the cofactor, and that their mobility is modulated by the anion bound at the phosphate site. Proteins 2007. © 2007 Wiley-Liss, Inc. IS - 3 JF - Proteins: Structure, Function, and Bioinformatics AD - Biocomputation and Complex Systems Physics Institute (BiFi), Universidad de Zaragoza, Unidad Asociada al IQFR-CSIC; Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain; Grupo de Cristalografía Molecular y Biología Estructural, Instituto Química-Física Rocasolano, Consejo Superior de Investigaciones Científicas, Serrano 119, 28006 Madrid, Spain; Departamento de Física de la Materia Condensada, Facultad de Ciencias, Universidad de Zaragoza EP - 594 TI - Common conformational changes in flavodoxins induced by FMN and anion binding: The structure of <I>Helicobacter pylori</I> apoflavodoxin VL - 69 SP - 581 KW - mios AU - Martínez-Júlvez, Marta AU - Cremades, Nunilo AU - Bueno, Marta AU - Pérez-Dorado, Inmaculada AU - Maya, Celia AU - Cuesta-López, Santiago AU - Prada-Gracia, Diego AU - Falo, Fernando AU - Hermoso, Juan AU - Sancho, Javier PY - 2007/// UR - http://dx.doi.org/10.1002/prot.21410 ER -