Kevin P Battaile

University of Kansas, Lawrence, KS, United States

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Publications (48)268.58 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: The 26S proteasome is a 2.5 MDa protease dedicated to the degradation of ubiquitinated proteins in eukaryotes. The assembly of this complex containing 66 polypeptides is assisted by at least nine proteasome-specific chaperones. One of these, Nas2, binds to the proteasomal AAA-ATPase subunit Rpt5. The PDZ domain of Nas2 binds to the C-terminal tail of Rpt5; however, it does not require the C-terminus of Rpt5 for binding. Here, the 1.15 Å resolution structure of the PDZ domain of Nas2 is reported. This structure will provide a basis for further insights regarding the structure and function of Nas2 in proteasome assembly.
    Acta crystallographica. Section F, Structural biology communications. 04/2014; 70(Pt 4):418-23.
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    ABSTRACT: The ubiquitous non-receptor protein tyrosine phosphatase SHP2 (encoded by PTPN11) plays a key role in RAS/ERK signaling downstream of most, if not all growth factors, cytokines and integrins, although its major substrates remain controversial. Mutations in PTPN11 lead to several distinct human diseases. Germ-line PTPN11 mutations cause about 50% of Noonan Syndrome (NS), which is among the most common autosomal dominant disorders. LEOPARD Syndrome (LS) is an acronym for its major syndromic manifestations: multiple Lentigines, Electrocardiographic abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of genitalia, Retardation of growth, and sensorineural Deafness. Frequently, LS patients have hypertrophic cardiomyopathy, and they might also have an increased risk of neuroblastoma (NS) and acute myeloid leukemia (AML). Consistent with the distinct pathogenesis of NS and LS, different types of PTPN11 mutations cause these disorders. Although multiple studies have reported the biochemical and biological consequences of NS- and LS-associated PTPN11 mutations, their structural consequences have not been analyzed fully. Here we report the crystal structures of WT SHP2 and five NS/LS-associated SHP2 mutants. These findings enable direct structural comparisons of the local conformational changes caused by each mutation. Our structural analysis agrees with, and provides additional mechanistic insight into, the previously reported catalytic properties of these mutants. The results of our research provide new information regarding the structure-function relationship of this medically important target, and should serve as a solid foundation for structure-based drug discovery programs.
    BMC Structural Biology 03/2014; 14(1):10. · 2.10 Impact Factor
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    ABSTRACT: Hemophores from Pseudomonas aeruginosa (HasAp), Serratia marcescens (HasAsm), and Yersinia pestis (HasAyp) bind hemin between two loops. One of the loops harbors conserved axial ligand Ty75 (Y75 loop) in all three structures, whereas the second loop (H32 loop) contains axial ligand His32 in HasAp and HasAsm, but a non-coordinating Gln32 in HasAyp. Hemin binding to the Y75 loop of HasAp or HasAsm causes a large rearrangement of the H32 loop that enables His32 coordination. The Q32 loop in apo-HasAyp is already in the closed conformation, such that hemin binding to the conserved Y75 loop occurs with minimal structural rearrangement and without coordinative interaction with the Q32 loop. In this study, structural and spectroscopic investigations of the hemophore HasAp were conducted to probe (i) the role of the conserved Tyr75 loop in hemin binding, and (ii) the proposed requirement of the His83-Tyr75 hydrogen bond to enable hemin coordination by Tyr75. High-resolution crystal structures of H83A holo-HasAp obtained at pH 6.5 (0.89 Å) and 5.4 (1.25 Å) show that Tyr75 remains coordinated to the heme iron, and that a water molecule can substitute for His83 Nδ to interact with the Oη atom of Tyr75, likely stabilizing the Tyr75-Fe interaction. NMR spectroscopy revealed that in apo-Y75A and H83A HasAp, the Y75 loop is disordered, and that disorder propagates to nearby elements of secondary structure, suggesting that the His83 Nδ to Tyr75 Oη interaction is important to the organization of the Y75 loop in apo-HasA. Kinetic analysis of hemin loading carried out with stopped flow UV-vis and rapid-freeze-quench resonance Raman show that both mutants load hemin with biphasic kinetic parameters that are not significantly dissimilar from those previously observed with wild type HasAp. When the structural and kinetic data are taken together a tentative model emerges, which suggests that HasA hemophores utilize hydrophobic, π-π stacking, and van der Waals interactions to load hemin efficiently, while axial ligation likely functions to slow hemin release, thus enabling the hemophore to meet the challenge of capturing hemin under inhospitable conditions and deliver it selectively to its cognate receptor.
    Biochemistry 03/2014; · 3.38 Impact Factor
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    ABSTRACT: The anthrax protective antigen (PA) is an 83 kDa protein that is one of three protein components of the anthrax toxin, an AB toxin secreted by Bacillus anthracis. PA is capable of undergoing several structural changes, including oligomerization to either a heptameric or octameric structure called the pre-pore, and at acidic pH undergoes a major conformational change to form a membrane spanning pore. In order to follow these structural changes at a residue-specific level, we have carried out initial studies where we have biosynthetically incorporated 5-fluorotryptophan (5-FTrp) into PA, and we have studied the influence of 5-FTrp labeling on the structural stability of PA and on binding to the host receptor capillary morphogenesis protein 2 (CMG2) using 19F-NMR. There are seven tryptophans in PA, but of the four domains in PA, only two contain tryptophans: domain 1 (Trp65, 90, 136, 206 and 226) and domain 2 (Trp346 and 477). Trp346 is of particular interest because of its close proximity to the CMG2 binding interface, and because it forms part of the membrane spanning pore. We show that the 19F resonance of Trp346 is sensitive to changes in pH, consistent with crystallographic studies, and that receptor binding significantly stabilizes Trp346 to both pH and temperature. In addition, we provide evidence which suggests that resonances from tryptophans distant from the binding interface, are also stabilized by the receptor. Our studies highlight the positive impact of receptor binding on protein stability, and the use of 19F-NMR in gaining insight into structural changes in a large molecular weight protein.
    Biochemistry 01/2014; · 3.38 Impact Factor
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    ABSTRACT: Asymmetric diadenosine 5',5'"-P1,P4-tetraphosphate (Ap4A) hydrolases are members of the Nudix superfamily that asymmetrically cleave the metabolite Ap4A into ATP and AMP while facilitating homeostasis. The obligate intracellular mammalian pathogen Chlamydia trachomatis possesses a single Nudix family protein, CT771. As pathogens that rely on a host for replication and dissemination typically have one or zero Nudix family proteins, this suggests that CT771 could be critical for chlamydial biology and pathogenesis. We identified orthologs to CT771 within environmental Chlamydiales that share active site residues suggesting a common function. Crystal structures of both apo- and ligand-bound CT771 were determined to 2.6 Å and 1.9 Å resolution, respectively. The structure of CT771 shows a αβα-sandwich motif with many conserved elements lining the putative Nudix active site. Numerous aspects of the ligand-bound CT771 structure mirror those observed in the ligand-bound structure of the Ap4A hydrolase from Caenorhabditis elegans. These structures represent only the second Ap4A hydrolase enzyme member determined from eubacteria and suggest that mammalian and bacterial Ap4A hydrolases might be more similar than previously thought. The aforementioned structural similarities, in tandem with molecular docking, guided the enzymatic characterization of CT771. Together, these studies provide the molecular details for substrate binding and specificity, supporting the analysis that CT771 is an Ap4A hydrolase (nudH).
    Biochemistry 12/2013; · 3.38 Impact Factor
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    ABSTRACT: The ability to selectively activate function of particular proteins via pharmacological agents is a longstanding goal in chemical biology. Recently, we reported an approach for designing a de novo allosteric effector site directly into the catalytic domain of an enzyme. This approach is distinct from traditional chemical rescue of enzymes in that it relies on disruption and restoration of structure, rather than active site chemistry, as a means to achieve modulate function. However, rationally identifying analogous de novo binding sites in other enzymes represents a key challenge for extending this approach to introduce allosteric control into other enzymes. Here we show that mutation sites leading to protein inactivation via tryptophan-to-glycine substitution and allowing (partial) reactivation by the subsequent addition of indole are remarkably frequent. Through a suite of methods including a cell-based reporter assay, computational structure prediction and energetic analysis, fluorescence studies, enzymology, pulse proteolysis, X-ray crystallography, and hydrogen-deuterium mass spectrometry, we find that these switchable proteins are most commonly modulated indirectly, through control of protein stability. Addition of indole in these cases rescues activity not by reverting a discrete conformational change, as we had observed in the sole previously reported example, but rather rescues activity by restoring protein stability. This important finding will dramatically impact the design of future switches and sensors built by this approach, since evaluating stability differences associated with cavity-forming mutations is a far more tractable task than predicting allosteric conformational changes. By analogy to natural signaling systems, the insights from this study further raise the exciting prospect of modulating stability to design optimal recognition properties into future de novo switches and sensors built through chemical rescue of structure.
    Journal of the American Chemical Society 12/2013; · 10.68 Impact Factor
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    ABSTRACT: Chlamydia trachomatis is a major cause of various diseases, including blinding trachoma and pelvic inflammatory disease, and is the leading reported sexually transmitted bacterial infection worldwide. All pathogenic Chlamydiae spp. utilize a supramolecular syringe, or type III secretion system (T3SS), to inject proteins into their obligate host in order to propagate infection. Here, the structure of CT584, a T3SS-associated protein, that has been refined to a resolution of 3.05 Å is reported. The CT584 structure is a hexamer comprised of a trimer of dimers. The structure shares a high degree of similarity to the recently reported structure of an orthologous protein, Cpn0803, from Chlamydia pneumoniae, which highlights the highly conserved nature of this protein across these chlamydial species, despite different tissue tropism and disease pathology.
    Acta Crystallographica Section F Structural Biology and Crystallization Communications 11/2013; 69(Pt 11):1196-201. · 0.55 Impact Factor
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    ABSTRACT: The proteasomal ATPase ring, comprising Rpt1-Rpt6, associates with the heptameric α-ring of the proteasome core particle (CP) in the mature proteasome, with the Rpt carboxy-terminal tails inserting into pockets of the α-ring. Rpt ring assembly is mediated by four chaperones, each binding a distinct Rpt subunit. Here we report that the base subassembly of the Saccharomyces cerevisiae proteasome, which includes the Rpt ring, forms a high-affinity complex with the CP. This complex is subject to active dissociation by the chaperones Hsm3, Nas6 and Rpn14. Chaperone-mediated dissociation was abrogated by a non-hydrolysable ATP analogue, indicating that chaperone action is coupled to nucleotide hydrolysis by the Rpt ring. Unexpectedly, synthetic Rpt tail peptides bound α-pockets with poor specificity, except for Rpt6, which uniquely bound the α2/α3-pocket. Although the Rpt6 tail is not visualized within an α-pocket in mature proteasomes, it inserts into the α2/α3-pocket in the base-CP complex and is important for complex formation. Thus, the Rpt-CP interface is reconfigured when the lid complex joins the nascent proteasome to form the mature holoenzyme.
    Nature 05/2013; · 38.60 Impact Factor
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    ABSTRACT: The human pathogen Yersinia pestis requires the assembly of the type III secretion system (T3SS) for virulence. The structural component of the T3SS contains an external needle and a tip complex, which is formed by LcrV in Y. pestis. The structure of an LcrV triple mutant (K40A/D41A/K42A) in a C273S background has previously been reported to 2.2 Å resolution. Here, the crystal structure of LcrV without the triple mutation in a C273S background is reported at a higher resolution of 1.65 Å. Overall the two structures are similar, but there are also notable differences, particularly near the site of the triple mutation. The refined structure revealed a slight shift in the backbone positions of residues Gly28-Asn43 and displayed electron density in the loop region consisting of residues Ile46-Val63, which was disordered in the original structure. In addition, the helical turn region spanning residues Tyr77-Gln95 adopts a different orientation.
    Acta Crystallographica Section F Structural Biology and Crystallization Communications 05/2013; 69(Pt 5):477-81. · 0.55 Impact Factor
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    ABSTRACT: Hemophores from Serratia marcescens (HasAsm) and Pseudomonas aeruginosa (HasAp) bind hemin between two loops, which harbor the axial ligands H32 and Y75. Hemin binding to the Y75 loop triggers closing of the H32 loop and enables binding of H32. Because Yersinia pestis HasA (HasAyp) presents a Gln at position 32, we determined the structures of apo- and holo-HasAyp. Surprisingly, the Q32 loop in apo-HasAyp is already in the closed conformation, but no residue from the Q32 loop binds hemin in holo-HasAyp. In agreement with the minimal reorganization between the apo- and holo-structures, the hemin on-rate is too fast to detect by conventional stopped-flow measurements.
    Biochemistry 04/2013; · 3.38 Impact Factor
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    ABSTRACT: Tail Assembly Chaperones (TACs) are a family of proteins likely required for the morphogenesis of all long-tailed phages. In this study, we determined the crystal structure of gp13, the TAC of phage HK97. This structure is similar that of the TAC from the Lactococcus phage p2, and two unannotated structures of likely TACs encoded in prophage-derived regions of B. subtilis and B. stearothermophilus. Despite the high sequence divergence of these proteins, gp13 forms a ring structure with similar dimensions to the spirals observed in the crystal lattices of these other proteins. Remarkably, these similar quaternary structures are formed through very different interprotomer interactions. We present functional data supporting the biological relevance of these spiral structures, and propose that spiral formation has been the primary requirement for these proteins during evolution. This study presents an unusual example of diverged protein sequences and oligomerization mechanisms in the presence of conserved quaternary structure.
    Journal of Molecular Biology 03/2013; · 3.91 Impact Factor
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    ABSTRACT: A conserved spiral structure for highly diverged phage Tail Assembly Chaperones, Journal of Molecular Biology (2013), doi:10.1016/j.jmb.2013.03.035 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
    Journal of Molecular Biology 03/2013; · 3.91 Impact Factor
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    ABSTRACT: A conserved spi-ral structure for highly diverged phage Tail Assembly Chaperones, Journal of Molecular Biology (2013), doi:10.1016/j.jmb.2013.03.035 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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    ABSTRACT: In this work we characterize an alcohol dehydrogenase (ADH) from the hyperthermophilic archaeon Pyrobaculum aerophilum (PyAeADHII). We have previously found that PyAeADHII has no activity when standard ADH substrates are used but is active when α-tetralone is used as substrate. Here, to gain insights into enzyme function, we screened several chemical libraries for enzymatic modulators using an assay employing α-tetralone. The results indicate that PyAeADHII activity in the presence of α-tetralone was inhibited by compounds such as flunarizine. We also examined metal coordination of the enzyme in solution by performing metal substitution of the enzyme-bound zinc (Zn(2+)) with cobalt. The solution-based absorption spectra for cobalt substituted PyAeADHII supports substitution at the structural Zn(2+) site. To gain structural insight, we obtained the crystal structure of both wild-type and cobalt-substituted PyAeADHII at 1.75 Å and 2.20 Å resolution, respectively. The X-ray data confirmed one metal ion per monomer present only at the structural site with otherwise close conservation to other ADH enzymes. We next determined the co-crystal structure of the NADPH-bound form of the enzyme at 2.35 Å resolution to help define the active site region of the enzyme and this data shows close structural conservation with horse ADH, despite the lack of a catalytic Zn(2+) ion in PyAeADHII. Modeling of α-tetralone into the NADPH bound structure suggests an arginine as a possible catalytic residue. The data presented here can yield a better understanding of alcohol dehydrogenases lacking the catalytic zinc as well as the structural features inherent to thermostable enzymes.
    PLoS ONE 01/2013; 8(6):e63828. · 3.73 Impact Factor
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    ABSTRACT: The nitrilases include a variety of enzymes with functional specificities of nitrilase, amidase, and hydrolase reactions. The crystal structure of the uncharacterized protein SA0302 from the pathogenic microorganism Staphylococcus aureus is solved at 1.7 Å resolution. The protein contains 261 amino acids and presents a four-layer αββα sandwich with a chain topology similar to that of a few known CN-hydrolase folds. In the crystal, the proteins are arranged as dimers whose monomers are related by a pseudo twofold rotation symmetry axis. Analysis of the sequences and structures of CN-hydrolases with known 3D structures shows that SA0302 definitely is a member of Branch 10 (Nit and NitFhit) of the nitrilase superfamily. Enzyme activities and substrate specificities of members of this branch are not yet characterized, in contrast to those of the members of Branches 1-9. Although the sequence identities between Branch 10 members are rather low, less than 30%, five conserved regions are common in this subfamily. Three of them contain functionally important catalytic residues, and the two other newly characterized ones are associated with crucial intramolecular and intermolecular interactions. Sequence homology of the area near the active site shows clearly that the catalytic triad of SA0302 is Glu41-Lys110-Cys146. We suggest also that the active site includes a fourth residue, the closely located Glu119. Despite an extensive similarity with other Nit-family structural folds, SA0302 displays an important difference. Protein loop 111-122, which follows the catalytic Lys110, is reduced to half the number of amino acids found in other Nit-family members. This leaves the active site fully accessible to solvent and substrates. We have identified conservative sequence motifs around the three core catalytic residues, which are inherent solely to Branch 10 of the nitrilase superfamily. On the basis of these new sequence fingerprints, 10 previously uncharacterized proteins also could be assigned to this hydrolase subfamily. An animated interactive 3D complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:19.
    Journal of biomolecular structure & dynamics 10/2012; · 4.99 Impact Factor
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    ABSTRACT: Adipose phospholipase A(2) (AdPLA or Group XVI PLA(2)) plays an important role in the onset of obesity by suppressing adipose tissue lipolysis. As a consequence, AdPLA-deficient mice are resistant to obesity induced by a high fat diet or leptin deficiency. It has been proposed that AdPLA mediates its antilipolytic effects by catalyzing the release of arachidonic acid. Based on sequence homology, AdPLA is part of a small family of acyltransferases and phospholipases related to lecithin:retinol acyltransferase (LRAT). To better understand the enzymatic mechanism of AdPLA and LRAT-related proteins, we solved the crystal structure of AdPLA. Our model indicates that AdPLA bears structural similarity to proteins from the NlpC/P60 family of cysteine proteases, having its secondary structure elements configured in a circular permutation of the classic papain fold. Using both structural and biochemical evidence, we demonstrate that the enzymatic activity of AdPLA is mediated by a distinctive Cys-His-His catalytic triad and that the C-terminal transmembrane domain of AdPLA is required for the interfacial catalysis. Analysis of the enzymatic activity of AdPLA toward synthetic and natural substrates indicates that AdPLA displays PLA(1) in addition to PLA(2) activity. Thus, our results provide insight into the enzymatic mechanism and biochemical properties of AdPLA and LRAT-related proteins and lead us to propose an alternate mechanism for AdPLA in promoting adipose tissue lipolysis that is not contingent on the release of arachidonic acid and that is compatible with its combined PLA(1)/A(2) activity.
    Journal of Biological Chemistry 08/2012; 287(42):35260-74. · 4.65 Impact Factor
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    ABSTRACT: Phylogenetic analysis has demonstrated that some positive-sense RNA viruses can be classified into the picornavirus-like supercluster, which includes picornaviruses, caliciviruses, and coronaviruses. These viruses possess 3C or 3C-like proteases (3Cpro or 3CLpro, respectively), which contain a typical chymotrypsin-like fold and a catalytic triad (or dyad) with a Cys residue as a nucleophile. The conserved key sites of 3Cpro or 3CLpro may serve as attractive targets for the design of broad-spectrum antivirals for multiple viruses in the supercluster. We previously reported the structure-based design and synthesis of potent protease inhibitors of Norwalk virus (NV), a member of the Caliciviridae family. We report herein the broad-spectrum antiviral activities of three compounds possessing a common dipeptidyl residue with different warheads, i.e., an aldehyde (GC373), a bisulfite adduct (GC376), and an α-ketoamide (GC375), against viruses that belong to the supercluster. All compounds were highly effective against the majority of tested viruses, with half-maximal inhibitory concentrations in the high nanomolar or low micromolar range in enzyme- and/or cell-based assays and with high therapeutic indices. We also report the high-resolution X-ray cocrystal structures of NV 3CLpro-, poliovirus 3Cpro-, and transmissible gastroenteritis virus 3CLpro- GC376 inhibitor complexes, which show the compound covalently bound to a nucleophilic Cys residue in the catalytic site of the corresponding protease. We conclude that these compounds have the potential to be developed as antiviral therapeutics aimed at a single virus or multiple viruses in the picornavirus-like supercluster by targeting 3Cpro or 3CLpro.
    Journal of Virology 08/2012; 86(21):11754-62. · 5.08 Impact Factor
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    ABSTRACT: The anthrax protective antigen (PA) binds to the host cellular receptor capillary morphogenesis protein 2 (CMG2) with high affinity. To gain a better understanding of how pH may affect binding to the receptor, we have investigated the kinetics of binding as a function of pH to the full-length monomeric PA and to two variants: a 2-fluorohistidine-labeled PA (2-FHisPA), which is ∼1 pH unit more stable to variations in pH than WT, and an ∼1 pH unit less stable variant in which Trp346 in the domain 2β(3) -2β(4) loop is substituted with a Phe (W346F). We show using stopped-flow fluorescence that the binding rate increases as the pH is lowered for all proteins, with little influence on the rate of dissociation. In addition, we have crystallized PA and the two variants and examine the influence of pH on structure. In contrast to previous X-ray studies, the domain 2β(3) -2β(4) loop undergoes little change in structure from pH ∼8 to 5.5 for the WT protein, but for the 2-FHis labeled and W346F mutant there are changes in structure consistent with previous X-ray studies. In accord with pH stability studies, we find that the average B-factor values increase by ∼20-30% for all three proteins at low pH. Our results suggest that for the full-length PA, low pH increases the binding affinity, likely through a change in structure that favors a more "bound-like" conformation.
    Protein Science 07/2012; 21(10):1467-80. · 2.74 Impact Factor
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    ABSTRACT: Ferritin-like molecules are unique to cellular iron homeostasis because they can store iron at concentrations much higher than those dictated by the solubility of Fe(3+). Very little is known about the protein interactions that deliver iron for storage or promote the mobilization of stored iron from ferritin-like molecules. Here, we report the X-ray crystal structure of Pseudomonas aeruginosa bacterioferritin (Pa-BfrB) in complex with bacterioferritin-associated ferredoxin (Pa-Bfd) at 2.0 Å resolution. As the first example of a ferritin-like molecule in complex with a cognate partner, the structure provides unprecedented insight into the complementary interface that enables the [2Fe-2S] cluster of Pa-Bfd to promote heme-mediated electron transfer through the BfrB protein dielectric (~18 Å), a process that is necessary to reduce the core ferric mineral and facilitate mobilization of Fe(2+). The Pa-BfrB-Bfd complex also revealed the first structure of a Bfd, thus providing a first view to what appears to be a versatile metal binding domain ubiquitous to the large Fer2_BFD family of proteins and enzymes with diverse functions. Residues at the Pa-BfrB-Bfd interface are highly conserved in Bfr and Bfd sequences from a number of pathogenic bacteria, suggesting that the specific recognition between Pa-BfrB and Pa-Bfd is of widespread significance to the understanding of bacterial iron homeostasis.
    Journal of the American Chemical Society 07/2012; 134(32):13470-81. · 10.68 Impact Factor
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    ABSTRACT: The chemical diversity of nature has tremendous potential for the discovery of molecular probes and medicinal agents. However, sensitivity of HTS assays to interfering components of crude extracts derived from plants, and macro- and microorganisms has curtailed their use in lead discovery. Here, we describe a process for leveraging the concentration-response curves obtained from quantitative HTS to improve the initial selection of "actives" from a library of partially fractionated natural product extracts derived from marine actinomycetes and fungi. By using pharmacological activity, the first-pass CRC paradigm improves the probability that labor-intensive subsequent steps of reculturing, extraction, and bioassay-guided isolation of active component(s) target the most promising strains and growth conditions. We illustrate how this process identified a family of fungal metabolites as potent inhibitors of firefly luciferase, subsequently resolved in molecular detail by X-ray crystallography.
    Chemistry & biology 11/2011; 18(11):1442-52. · 6.52 Impact Factor

Publication Stats

378 Citations
364 Downloads
268.58 Total Impact Points

Institutions

  • 2010–2013
    • University of Kansas
      • • Department of Chemistry
      • • Ralph N. Adams Institute for Bioanalytical Chemistry
      Lawrence, KS, United States
    • Argonne National Laboratory
      Lemont, Illinois, United States
    • University Health Network
      Toronto, Ontario, Canada
  • 2011–2012
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2002–2004
    • Medical College of Wisconsin
      • Department of Biochemistry
      Milwaukee, WI, United States
  • 1996–1998
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States