http://www.biomedcentral.com/bmcstructbiol/ The editor's pick of recent articles published by BMC Structural Biology 2012-05-17T00:00:00Z Small-angle scattering is becoming an increasingly popular tool for the study of bio-molecular structures in solution. The large number of publications with 3D-structural models generated from small-angle solution scattering data has led to a growing consensus for the need to establish a standard reporting framework for their publication. The International Union of Crystallography recently established a set of guidelines for the necessary information required for the publication of such structural models. Here we describe the rationale for these guidelines and the importance of standardising the way in which small-angle scattering data from bio-molecules and associated structural interpretations are reported. http://www.biomedcentral.com/1472-6807/12/9 David A Jacques Jules M Guss Jill Trewhella BMC Structural Biology 2012, 12:9 2012-05-17T00:00:00Z 10.1186/1472-6807-12-9 Setting the standard for SAS Jill Trewhella and colleagues describe the rationale behind guidelines recently issued by The International Union of Crystallography for the reporting of biomolecular structures derived from Small-Angle Scattering (SAS) data. /content/figures/1472-6807-12-9-toc.gif BMC Structural Biology 1472-6807 12 9 2012-05-17T00:00:00Z PDF Background: Influenza neuraminidase (NA) is an important target for antiviral inhibitors since its active site is highly conserved such that inhibitors can be cross-reactive against multiple types and subtypes of influenza. Here, we discuss the crystal structure of neuraminidase subtype N9 complexed with a new benzoic acid based inhibitor (2) that was designed to add contacts by overpacking one side of the active site pocket. Inhibitor 2 uses benzoic acid to mimic the pyranose ring, a bis-(hydroxymethyl)-substituted 2-pyrrolidinone ring in place of the N-acetyl group of the sialic acid, and a branched aliphatic structure to fill the sialic acid C6 subsite. Results: Inhibitor 2 {4-[2,2-bis(hydroxymethyl)-5-oxo-pyrrolidin-1-yl]-3-[(dipropylamino)methyl)]benzoic acid} was soaked into crystals of neuraminidase of A/tern/Australia/G70c/75 (N9), and the structure refined with 1.55 A X-ray data. The benzene ring of the inhibitor tilted 8.9degrees compared to the previous compound (1), and the number of contacts, including hydrogen bonds, increased. However, the IC50 for compound 2 remained in the low micromolar range, likely because one propyl group was disordered.In this high-resolution structure of NA isolated from virus grown in chicken eggs, we found electron density for additional sugar units on the N-linked glycans compared to previous neuraminidase structures. In particular, seven mannoses and two N-acetylglucosamines are visible in the glycan attached to Asn200. This long, branched high-mannose glycan makes significant contacts with the neighboring subunit. Conclusions: We designed inhibitor 2 with an extended substituent at C4 corresponding to C6 of sialic acid to increase the contact surface in the C6-subsite and to force the benzene ring to tilt to maximize these interactions while retaining the interactions of the carboxylate and the pyrolidinone substituents. The crystal structure at 1.55 A showed that we partially succeeded in that the ring in 2 is tilted relative to 1 and the number of contacts increased, but one hydrophobic branch makes no contacts, perhaps explaining why the IC50 did not decrease. Future design efforts will include branches of unequal length so that both branches may be accommodated in the C6-subsite without conformational disorder.The high-mannose glycan attached to Asn200 makes several inter-subunit contacts and appears to stabilize the tetramer. http://www.biomedcentral.com/1472-6807/12/7 Lalitha Venkatramani Eric S Johnson Gundarao Kolavi Gillian M Air Wayne J Brouillette Blaine HM Mooers BMC Structural Biology 2012, 12:7 2012-05-06T00:00:00Z 10.1186/1472-6807-12-7 Tilting influenza neuraminidase inhibitors The crystal structure of a novel benzoic acid inhibitor of influenza neuraminidase reveals an increased number of contacts compared to previous inhibitors, due to a tilt in the position of the benzene ring that maximizes these interactions. /content/figures/1472-6807-12-7-toc.gif BMC Structural Biology 1472-6807 12 7 2012-05-06T00:00:00Z PDF Background: Plasmodium falciparum is the protozoan parasite primarily responsible for more than one million malarial deaths, annually, and is developing resistance to current therapies. Throughout its lifespan, the parasite is subjected to oxidative attack, so Plasmodium antioxidant defences are essential for its survival and are targets for disease control. Results: To further understand the molecular aspects of the Plasmodium redox system, we solved 4 structures of Plasmodium peroxiredoxins (Prx). Our study has confirmed PvTrx-Px1 to be a hydrogen peroxide (H2O2)-sensitive peroxiredoxin. We have identified and characterized the novel toroid octameric oligomer of PyTrx-Px1, which may be attributed to the interplay of several factors including: (1) the orientation of the conserved surface/buried arginine of the NNLA(I/L)GRS-loop; and (2) the C-terminal tail positioning (also associated with the aforementioned conserved loop) which facilitates the intermolecular hydrogen bond between dimers (in an A-C fashion). In addition, a notable feature of the disulfide bonds in some of the Prx crystal structures is discussed. Finally, insight into the latter stages of the peroxiredoxin reaction coordinate is gained. Our structure of PyPrx6 is not only in the sulfinic acid (RSO2H) form, but it is also with glycerol bound in a way (not previously observed) indicative of product binding. Conclusions: The structural characterization of Plasmodium peroxiredoxins provided herein provides insight into their oligomerization and product binding which may facilitate the targeting of these antioxidant defences. Although the structural basis for the octameric oligomerization is further understood, the results yield more questions about the biological implications of the peroxiredoxin oligomerization, as multiple toroid configurations are now known. The crystal structure depicting the product bound active site gives insight into the overoxidation of the active site and allows further characterization of the leaving group chemistry. http://www.biomedcentral.com/1472-6807/12/2 Wei Qiu Aiping Dong Juan C Pizarro Alexei Botchkarsev Jinrong Min Amy K Wernimont Tanya Hills Raymond Hui Jennifer D Artz BMC Structural Biology 2012, 12:2 2012-03-19T00:00:00Z 10.1186/1472-6807-12-2 Oligomerization of Plasmodium peroxiredoxins Structural characterization of peroxiredoxins from Plasmodium species identifies the novel toroid octameric oligomer of PyTrx-Px1 and confirms that PvTrx-Px1 is a hydrogen peroxide-sensitive peroxiredoxin, which may aid targeting of these antioxidant enzymes in drug design /content/figures/1472-6807-12-2-toc.gif BMC Structural Biology 1472-6807 12 2 2012-03-19T00:00:00Z XML Background: Protein-DNA interactions play a crucial role in the life of biological organisms in controlling transcription, regulation, as well as DNA recombination and repair. The deep understanding of these processes, which requires the atomic description of the interactions occurring between the proteins and their DNA partners is often limited by the absence of a 3D structure of such complexes. Results: In this study, using a method combining sequence homology, structural analogy modeling and biochemical data, we first build the 3D structure of the complex between the poorly-characterized PerR-like regulator Slr1738 and its target DNA, which controls the defences against metal and oxidative stresses in Synechocystis. In a second step, we propose an expanded version of the Slr1738-DNA structure, which accommodates the DNA binding of Slr1738 multimers, a feature likely operating in the complex Slr1738-mediated regulation of stress responses. Finally, in agreement with experimental data we present a 3D-structure of the Slr1738-DNA complex resulting from the binding of multimers of the FUR-like regulator onto its target DNA that possesses internal repeats. Conclusion: Using a combination of different types of data, we build and validate a relevant model of the tridimensional structure of a biologically important protein-DNA complex. Then, based on published observations, we propose more elaborated multimeric models that may be biologically important to understand molecular mechanisms. http://www.biomedcentral.com/1472-6807/12/1 Paul Garcin Olivier Delalande Ju-Yuan Zhang Corinne Cassier-Chauvat Franck Chauvat Yves Boulard BMC Structural Biology 2012, 12:1 2012-01-30T00:00:00Z 10.1186/1472-6807-12-1 Modeling protein/DNA complexes in cyanobacteria A 3D structure of the complex between the PerR-like regulator Slr1738 and its target DNA, which controls metal and oxidative stress response in the cyanobaterium Synechocystis, provides insight into stability and recognition in protein-DNA interactions /content/figures/1472-6807-12-1-toc.gif BMC Structural Biology 1472-6807 12 1 2012-01-30T00:00:00Z XML Background: Cyclophilin A (CypA) represents a potential key molecule in future antiretroviral therapy since inhibition of CypA suppresses human immunodeficiency virus type 1 (HIV-1) replication. CypA interacts with the virus proteins Capsid (CA) and Vpr, however, the mechanism through which CypA influences HIV-1 infectivity still remains unclear. Results: Here the interaction of full-length HIV-1 Vpr with the host cellular factor CypA has been characterized and quantified by surface plasmon resonance spectroscopy. A C-terminal region of Vpr, comprising the 16 residues 75GCRHSRIGVTRQRRAR90, with high binding affinity for CypA has been identified. This region of Vpr does not contain any proline residues but binds much more strongly to CypA than the previously characterized N-terminal binding domain of Vpr, and is thus the first protein binding domain to CypA described involving no proline residues. The fact that the mutant peptide Vpr75-90 R80A binds more weakly to CypA than the wild-type peptide confirms that Arg-80 is a key residue in the C-terminal binding domain. The N- and C-terminal binding regions of full-length Vpr bind cooperatively to CypA and have allowed a model of the complex to be created. The dissociation constant of full-length Vpr to CypA was determined to be approximately 320 nM, indicating that the binding may be stronger than that of the well characterized interaction of HIV-1 CA with CypA. Conclusions: For the first time the interaction of full-length Vpr and CypA has been characterized and quantified. A non-proline-containing 16-residue region of C-terminal Vpr which binds specifically to CypA with similar high affinity as full-length Vpr has been identified. The fact that this is the first non-proline containing binding motif of any protein found to bind to CypA, changes the view on how CypA is able to interact with other proteins. It is interesting to note that several previously reported key functions of HIV-1 Vpr are associated with the identified N- and C-terminal binding domains of the protein to CypA. http://www.biomedcentral.com/1472-6807/11/49 Sara MØ Solbak Victor Wray Ole Horvli Arnt J Raae Marte I Flydal Petra Henklein Peter Henklein Manfred Nimtz Ulrich Schubert Torgils Fossen BMC Structural Biology 2011, 11:49 2011-12-20T00:00:00Z 10.1186/1472-6807-11-49 Novel non-proline-containing CypA binding motif Identification of a region of HIV-1 Vpr which binds specifically to the host cellular factor CypA with similar affinity to full-length Vpr is the first such binding domain described that involves no proline residues. /content/figures/1472-6807-11-49-toc.gif BMC Structural Biology 1472-6807 11 49 2011-12-20T00:00:00Z XML