BMC Structural Biology最新文献

{"title":"Reliable structural interpretation of small-angle scattering data from bio-molecules in solution - the importance of quality control and a standard reporting framework","authors":"David A Jacques,&nbsp;Jules Mitchell Guss,&nbsp;Jill Trewhella","doi":"10.1186/1472-6807-12-9","DOIUrl":"https://doi.org/10.1186/1472-6807-12-9","url":null,"abstract":"<p>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.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2012-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4695131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A structural model of the E. coli PhoB Dimer in the transcription initiation complex","authors":"Chang-Shung Tung,&nbsp;Benjamin H McMahon","doi":"10.1186/1472-6807-12-3","DOIUrl":"https://doi.org/10.1186/1472-6807-12-3","url":null,"abstract":"<p>There exist &gt; 78,000 proteins and/or nucleic acids structures that were determined experimentally. Only a small portion of these structures corresponds to those of protein complexes. While homology modeling is able to exploit knowledge-based potentials of side-chain rotomers and backbone motifs to infer structures for new proteins, no such general method exists to extend our understanding of protein interaction motifs to novel protein complexes.</p><p>We use a Motif Binding Geometries (MBG) approach, to infer the structure of a protein complex from the database of complexes of homologous proteins taken from other contexts (such as the helix-turn-helix motif binding double stranded DNA), and demonstrate its utility on one of the more important regulatory complexes in biology, that of the RNA polymerase initiating transcription under conditions of phosphate starvation. The modeled PhoB/RNAP/σ-factor/DNA complex is stereo-chemically reasonable, has sufficient interfacial Solvent Excluded Surface Areas (SESAs) to provide adequate binding strength, is physically meaningful for transcription regulation, and is consistent with a variety of known experimental constraints.</p><p>Based on a straightforward and easy to comprehend concept, \"proteins and protein domains that fold similarly could interact similarly\", a structural model of the PhoB dimer in the transcription initiation complex has been developed. This approach could be extended to enable structural modeling and prediction of other bio-molecular complexes. Just as models of individual proteins provide insight into molecular recognition, catalytic mechanism, and substrate specificity, models of protein complexes will provide understanding into the combinatorial rules of cellular regulation and signaling.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2012-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4794186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structures from the Plasmodium peroxiredoxins: new insights into oligomerization and product binding","authors":"Wei Qiu,&nbsp;Aiping Dong,&nbsp;Juan C Pizarro,&nbsp;Alexei Botchkarsev,&nbsp;Jinrong Min,&nbsp;Amy K Wernimont,&nbsp;Tanya Hills,&nbsp;Raymond Hui,&nbsp;Jennifer D Artz","doi":"10.1186/1472-6807-12-2","DOIUrl":"https://doi.org/10.1186/1472-6807-12-2","url":null,"abstract":"<p><i>Plasmodium falciparum</i> 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 <i>Plasmodium</i> antioxidant defences are essential for its survival and are targets for disease control.</p><p>To further understand the molecular aspects of the <i>Plasmodium</i> redox system, we solved 4 structures of <i>Plasmodium</i> peroxiredoxins (Prx). Our study has confirmed <i>Pv</i> Trx-Px1 to be a hydrogen peroxide (H₂O₂)-sensitive peroxiredoxin. We have identified and characterized the novel toroid octameric oligomer of <i>Py</i> Trx-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 <i>C</i>-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 <i>Py</i> Prx6 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.</p><p>The structural characterization of <i>Plasmodium</i> 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.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"12 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2012-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-12-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4757738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Host-Pathogen interaction of human cyclophilin A and HIV-1 Vpr requires specific N-terminal and novel C-terminal domains","authors":"Sara MØ Solbak,&nbsp;Victor Wray,&nbsp;Ole Horvli,&nbsp;Arnt J Raae,&nbsp;Marte I Flydal,&nbsp;Petra Henklein,&nbsp;Peter Henklein,&nbsp;Manfred Nimtz,&nbsp;Ulrich Schubert,&nbsp;Torgils Fossen","doi":"10.1186/1472-6807-11-49","DOIUrl":"https://doi.org/10.1186/1472-6807-11-49","url":null,"abstract":"<p>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.</p><p>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 Vpr^75-90 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.</p><p>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.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2011-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-49","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4780974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural comparison of tRNA m1A58 methyltransferases revealed different molecular strategies to maintain their oligomeric architecture under extreme conditions","authors":"Amandine Guelorget,&nbsp;Pierre Barraud,&nbsp;Carine Tisné,&nbsp;Béatrice Golinelli-Pimpaneau","doi":"10.1186/1472-6807-11-48","DOIUrl":"https://doi.org/10.1186/1472-6807-11-48","url":null,"abstract":"<p>tRNA m¹A58 methyltransferases (TrmI) catalyze the transfer of a methyl group from S-adenosyl-L-methionine to nitrogen 1 of adenine 58 in the T-loop of tRNAs from all three domains of life. The m¹A58 modification has been shown to be essential for cell growth in yeast and for adaptation to high temperatures in thermophilic organisms. These enzymes were shown to be active as tetramers. The crystal structures of five TrmIs from hyperthermophilic archaea and thermophilic or mesophilic bacteria have previously been determined, the optimal growth temperature of these organisms ranging from 37°C to 100°C. All TrmIs are assembled as tetramers formed by dimers of tightly assembled dimers.</p><p>In this study, we present a comparative structural analysis of these TrmIs, which highlights factors that allow them to function over a large range of temperature. The monomers of the five enzymes are structurally highly similar, but the inter-monomer contacts differ strongly. Our analysis shows that bacterial enzymes from thermophilic organisms display additional intermolecular ionic interactions across the dimer interfaces, whereas hyperthermophilic enzymes present additional hydrophobic contacts. Moreover, as an alternative to two bidentate ionic interactions that stabilize the tetrameric interface in all other TrmI proteins, the tetramer of the archaeal <i>P. abyssi</i> enzyme is strengthened by four intersubunit disulfide bridges.</p><p>The availability of crystal structures of TrmIs from mesophilic, thermophilic or hyperthermophilic organisms allows a detailed analysis of the architecture of this protein family. Our structural comparisons provide insight into the different molecular strategies used to achieve the tetrameric organization in order to maintain the enzyme activity under extreme conditions.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2011-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-48","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4564403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A conformation ensemble approach to protein residue-residue contact","authors":"Jesse Eickholt,&nbsp;Zheng Wang,&nbsp;Jianlin Cheng","doi":"10.1186/1472-6807-11-38","DOIUrl":"https://doi.org/10.1186/1472-6807-11-38","url":null,"abstract":"<p>Protein residue-residue contact prediction is important for protein model generation and model evaluation. Here we develop a conformation ensemble approach to improve residue-residue contact prediction. We collect a number of structural models stemming from a variety of methods and implementations. The various models capture slightly different conformations and contain complementary information which can be pooled together to capture recurrent, and therefore more likely, residue-residue contacts.</p><p>We applied our conformation ensemble approach to free modeling targets from both CASP8 and CASP9. Given a diverse ensemble of models, the method is able to achieve accuracies of. 48 for the top <i>L</i>/5 medium range contacts and. 36 for the top <i>L</i>/5 long range contacts for CASP8 targets (<i>L</i> being the target domain length). When applied to targets from CASP9, the accuracies of the top <i>L</i>/5 medium and long range contact predictions were. 34 and. 30 respectively.</p><p>When operating on a moderately diverse ensemble of models, the conformation ensemble approach is an effective means to identify medium and long range residue-residue contacts. An immediate benefit of the method is that when tied with a scoring scheme, it can be used to successfully rank models.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2011-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-38","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4512420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel dimeric β-helical model of an ice nucleation protein with bridged active sites","authors":"Christopher P Garnham,&nbsp;Robert L Campbell,&nbsp;Virginia K Walker,&nbsp;Peter L Davies","doi":"10.1186/1472-6807-11-36","DOIUrl":"https://doi.org/10.1186/1472-6807-11-36","url":null,"abstract":"<p>Ice nucleation proteins (INPs) allow water to freeze at high subzero temperatures. Due to their large size (&gt;120 kDa), membrane association, and tendency to aggregate, an experimentally-determined tertiary structure of an INP has yet to be reported. How they function at the molecular level therefore remains unknown.</p><p>Here we have predicted a novel β-helical fold for the INP produced by the bacterium <i>Pseudomonas borealis</i>. The protein uses internal serine and glutamine ladders for stabilization and is predicted to dimerize via the burying of a solvent-exposed tyrosine ladder to make an intimate hydrophobic contact along the dimerization interface. The manner in which <i>Pb</i> INP dimerizes also allows for its multimerization, which could explain the aggregation-dependence of INP activity. Both sides of the <i>Pb</i> INP structure have tandem arrays of amino acids that can organize waters into the ice-like clathrate structures seen on antifreeze proteins.</p><p>Dimerization dramatically increases the 'ice-active' surface area of the protein by doubling its width, increasing its length, and presenting identical ice-forming surfaces on both sides of the protein. We suggest that this allows sufficient anchored clathrate waters to align on the INP surface to nucleate freezing. As <i>Pb</i> INP is highly similar to all known bacterial INPs, we predict its fold and mechanism of action will apply to these other INPs.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2011-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-36","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5062448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of functionally important residues in globular proteins from unusual central distances of amino acids","authors":"Marek Kochańczyk","doi":"10.1186/1472-6807-11-34","DOIUrl":"https://doi.org/10.1186/1472-6807-11-34","url":null,"abstract":"<p>Well-performing automated protein function recognition approaches usually comprise several complementary techniques. Beside constructing better consensus, their predictive power can be improved by either adding or refining independent modules that explore orthogonal features of proteins. In this work, we demonstrated how the exploration of global atomic distributions can be used to indicate functionally important residues.</p><p>Using a set of carefully selected globular proteins, we parametrized continuous probability density functions describing preferred central distances of individual protein atoms. Relative preferred burials were estimated using mixture models of radial density functions dependent on the amino acid composition of a protein under consideration. The unexpectedness of extraordinary locations of atoms was evaluated in the information-theoretic manner and used directly for the identification of key amino acids. In the validation study, we tested capabilities of a tool built upon our approach, called SurpResi, by searching for binding sites interacting with ligands. The tool indicated multiple candidate sites achieving success rates comparable to several geometric methods. We also showed that the unexpectedness is a property of regions involved in protein-protein interactions, and thus can be used for the ranking of protein docking predictions. The computational approach implemented in this work is freely available via a Web interface at http://www.bioinformatics.org/surpresi.</p><p>Probabilistic analysis of atomic central distances in globular proteins is capable of capturing distinct orientational preferences of amino acids as resulting from different sizes, charges and hydrophobic characters of their side chains. When idealized spatial preferences can be inferred from the sole amino acid composition of a protein, residues located in hydrophobically unfavorable environments can be easily detected. Such residues turn out to be often directly involved in binding ligands or interfacing with other proteins.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2011-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-34","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4735817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptide binding prediction for the human class II MHC allele HLA-DP2: a molecular docking approach","authors":"Atanas Patronov,&nbsp;Ivan Dimitrov,&nbsp;Darren R Flower,&nbsp;Irini Doytchinova","doi":"10.1186/1472-6807-11-32","DOIUrl":"https://doi.org/10.1186/1472-6807-11-32","url":null,"abstract":"<p>MHC class II proteins bind oligopeptide fragments derived from proteolysis of pathogen antigens, presenting them at the cell surface for recognition by CD4+ T cells. Human MHC class II alleles are grouped into three loci: HLA-DP, HLA-DQ and HLA-DR. In contrast to HLA-DR and HLA-DQ, HLA-DP proteins have not been studied extensively, as they have been viewed as less important in immune responses than DRs and DQs. However, it is now known that HLA-DP alleles are associated with many autoimmune diseases. Quite recently, the X-ray structure of the HLA-DP2 molecule (DPA*0103, DPB1*0201) in complex with a self-peptide derived from the HLA-DR α-chain has been determined. In the present study, we applied a validated molecular docking protocol to a library of 247 modelled peptide-DP2 complexes, seeking to assess the contribution made by each of the 20 naturally occurred amino acids at each of the nine binding core peptide positions and the four flanking residues (two on both sides).</p><p>The free binding energies (FBEs) derived from the docking experiments were normalized on a position-dependent (npp) and on an overall basis (nap), and two docking score-based quantitative matrices (DS-QMs) were derived: QMnpp and QMnap. They reveal the amino acid preferences at each of the 13 positions considered in the study. Apart from the leading role of anchor positions p1 and p6, the binding to HLA-DP2 depends on the preferences at p2. No effect of the flanking residues was found on the peptide binding predictions to DP2, although all four of them show strong preferences for particular amino acids. The predictive ability of the DS-QMs was tested using a set of 457 known binders to HLA-DP2, originating from 24 proteins. The sensitivities of the predictions at five different thresholds (5%, 10%, 15%, 20% and 25%) were calculated and compared to the predictions made by the NetMHCII and IEDB servers. Analysis of the DS-QMs indicated an improvement in performance. Additionally, DS-QMs identified the binding cores of several known DP2 binders.</p><p>The molecular docking protocol, as applied to a combinatorial library of peptides, models the peptide-HLA-DP2 protein interaction effectively, generating reliable predictions in a quantitative assessment. The method is structure-based and does not require extensive experimental sequence-based data. Thus, it is universal and can be applied to model any peptide - protein interaction.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2011-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-32","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4570908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystallographic analysis reveals the structural basis of the high-affinity binding of iophenoxic acid to human serum albumin","authors":"Ali J Ryan,&nbsp;Chun-wa Chung,&nbsp;Stephen Curry","doi":"10.1186/1472-6807-11-18","DOIUrl":"https://doi.org/10.1186/1472-6807-11-18","url":null,"abstract":"<p>Iophenoxic acid is an iodinated radiocontrast agent that was withdrawn from clinical use because of its exceptionally long half-life in the body, which was due in part to its high-affinity binding to human serum albumin (HSA). It was replaced by Iopanoic acid, which has an amino rather than a hydroxyl group at position 3 on the iodinated benzyl ring and, as a result, binds to albumin with lower affinity and is excreted more rapidly from the body. To understand how iophenoxic acid binds so tightly to albumin, we wanted to examine the structural basis of its interaction with HSA.</p><p>We have determined the co-crystal structure of HSA in complex with iophenoxic acid at 2.75 ? resolution, revealing a total of four binding sites, two of which - in drugs sites 1 and 2 on the protein - are likely to be occupied at clinical doses. High-affinity binding of iophenoxic acid occurs at drug site 1. The structure reveals that polar and apolar groups on the compound are involved in its interactions with drug site 1. In particular, the 3-hydroxyl group makes three hydrogen bonds with the side-chains of Tyr 150 and Arg 257. The mode of binding to drug site 2 is similar except for the absence of a binding partner for the hydroxyl group on the benzyl ring of the compound.</p><p>The HSA-iophenoxic acid structure indicates that high-affinity binding to drug site 1 is likely to be due to extensive desolvation of the compound, coupled with the ability of the binding pocket to provide a full set of salt-bridging or hydrogen bonding partners for its polar groups. Consistent with this interpretation, the structure also suggests that the lower-affinity binding of iopanoic acid arises because replacement of the 3-hydroxyl by an amino group eliminates hydrogen bonding to Arg 257. This finding underscores the importance of polar interactions in high-affinity binding to albumin.</p>","PeriodicalId":498,"journal":{"name":"BMC Structural Biology","volume":"11 1","pages":""},"PeriodicalIF":2.222,"publicationDate":"2011-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1472-6807-11-18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4706951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}