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At least 1,657 records · Page 92Linked to original sources
PubMed2000

The three-dimensional structure of a complex of a murine Fab (NC10. 14) with a potent sweetener (NC174): an illustration of structural diversity in antigen recognition by immunoglobulins.

The three-dimensional structure of a complex of an Fab from a murine IgG2b(lambda) antibody (NC10.14) with a high potency sweet tasting hap- ten, N-(p-cyanophenyl)-N'-(diphenylmethyl)-N"-(carboxymethyl)guan idine (NC174), has been determined to 2.6 A resolution by X-ray crystallography. This complex crystallized in the triclinic space group P1, with two molecules in the asymmetric unit. In contrast to a companion monoclonal antibody (NC6.8) with a kappa-type light chain and similar high affinity for the NC174 ligand, the NC10.14 antibody possessed a large and deep antigen combining site bounded primarily by the third complementarity-determining regions (CDR3s) of the light and heavy chains. CDR3 of the heavy chain dominated the site and its crown protruded into the external solvent as a type 1' beta-turn. NC174 was nested against HCDR3 and was held in place by two tryptophan side-chains (L91 and L96) from LCDR3. The diphenyl rings were accommodated on an upper tier of the binding pocket that is largely hydrophobic. At the floor of the site, a positively charged arginine side-chain (H95) stabilized the orientation of the electronegative cyano group of the hapten. The negative charge on the acetate group was partially neutralized by a hydrogen bond with the phenolic hydroxyl group of tyrosine H58. Comparisons of the modes of binding of NC174 to the NC6.8 and NC10.14 antibodies illustrate the enormous structural and mechanistic diversity manifest by immune responses.

Amino Acid Sequence↗
PubMed2001

X-ray structure analysis and crystallographic refinement of lumazine synthase from the hyperthermophile Aquifex aeolicus at 1.6 A resolution: determinants of thermostability revealed from structural comparisons.

An open reading frame optimized for expression of 6,7-dimethyl-8-ribityl-lumazine synthase of the hyperthermophilic bacterium Aquifex aeolicus in Escherichia coli was synthesized and expressed in a recombinant E. coli strain to a level of around 15 %. The recombinant protein was purified by heat-treatment and gel-filtration. The protein was crystallized in the cubic space group I23 with the cell dimensions a = b = c = 180.8 A, and diffraction data were collected to 1.6 A resolution. The structure was solved by molecular replacement using lumazine synthase from Bacillus subtilis as search model. The structure of the A. aeolicus enzyme was refined to a resolution of 1.6 A. The spherical protein consists of 60 identical subunits with strict icosahedral 532 symmetry. The subunit fold is closely related to that of the B. subtilis enzyme (rmsd 0.80 A). The extremely thermostable lumazine synthase from A. aeolicus has a melting temperature of 119.9 degrees C. Compared to other icosahedral and pentameric lumazine synthases, the A. aeolicus enzyme has the largest accessible surface presented by charged residues and the smallest surface presented by hydrophobic residues. It also has the largest number of ion-pairs per subunit. Two ion-pair networks involving two, respectively three, stacking arginine residues assume a distinct role in linking adjacent subunits. The findings indicate the influence of the optimization of hydrophobic and ionic contacts in gaining thermostability.

Amino Acid Sequence↗
PubMed2001

The high-resolution X-ray crystallographic structure of the ferritin (EcFtnA) of Escherichia coli; comparison with human H ferritin (HuHF) and the structures of the Fe(3+) and Zn(2+) derivatives.

The high-resolution structure of the non-haem ferritin from Escherichia coli (EcFtnA) is presented together with those of its Fe(3+) and Zn(2+) derivatives, this being the first high-resolution X-ray analysis of the iron centres in any ferritin. The binding of both metals is accompanied by small changes in the amino acid ligand positions. Mean Fe(A)(3+)-Fe(B)(3+) and Zn(A)(2+)-Zn(B)(2+) distances are 3.24 A and 3.43 A, respectively. In both derivatives, metal ions at sites A and B are bridged by a glutamate side-chain (Glu50) in a syn-syn conformation. The Fe(3+) derivative alone shows a third metal site (Fe( C)( 3+)) joined to Fe(B)(3+) by a long anti-anti bidentate bridge through Glu130 (mean Fe(B)(3+)-Fe(C)(3+) distance 5.79 A). The third metal site is unique to the non-haem bacterial ferritins. The dinuclear site lies at the inner end of a hydrophobic channel connecting it to the outside surface of the protein shell, which may provide access for dioxygen and possibly for metal ions shielded by water. Models representing the possible binding mode of dioxygen to the dinuclear Fe(3+) pair suggest that a gauche micro-1,2 mode may be preferred stereochemically. Like those of other ferritins, the 24 subunits of EcFtnA are folded as four-helix bundles that assemble into hollow shells and both metals bind at dinuclear centres in the middle of the bundles. The structural similarity of EcFtnA to the human H chain ferritin (HuHF) is remarkable (r.m.s. deviation of main-chain atoms 0.66 A) given the low amino acid sequence identity (22 %). Many of the conserved residues are clustered at the dinuclear centre but there is very little conservation of residues making inter-subunit interactions.

Amino Acid Sequence↗
PubMed2001

The crystal structure of the influenza matrix protein M1 at neutral pH: M1-M1 protein interfaces can rotate in the oligomeric structures of M1.

The influenza matrix protein (M1) forms a protein layer under the viral membrane and is essential for viral stability and integrity. M1 mediates the encapsidation of the viral RNPs into the viral membrane by its membrane and RNP-binding activities. In order to understand the roles of M1-M1 protein interactions in forming the M1 layer, X-ray crystallographic studies of a M1 fragment (1-162) were carried out at neutral pH and compared with an acidic pH structure. At neutral pH the asymmetric unit was a stacked dimer of M1. A long molecular ribbon of neutral stacked dimers was formed by translation as dictated by the P1 space group. The elongated ribbon had a positively charged stripe on one side of the ribbon. A similar M1-M1 stacking interface was also found in the acidic asymmetric unit. However, within the acidic stacked dimer the molecules were not straight, but rotated in relation to each other by slightly changing the M1-M1 stacking interface. The acidic structure possessed an additional M1-M1 twofold interface. Protein docking confirmed that the M1-M1 stacking and M1-M1 twofold interfaces could be used to form a double ribbon of M1 molecules. By iterative repetition of the rotated relationship among the M1 molecules, a helix of M1 was generated. These studies suggest that M1 has the ability to form straight or bent elongated ribbons and helices. These oligomers are consistent with previous electron microscopic studies of M1, which demonstrated that isolated M1 formed elongated and flexible ribbons when isolated from what appeared to be a helical shell of M1 in the influenza virus.

Crystallography, X-Ray↗
PubMed2006

Crystal structure of human dynein light chain Dnlc2A: structural insights into the interaction with IC74.

The human light chain of the motor protein dynein, Dnlc2A, is also a novel TGF-beta-signaling component, which is altered with high frequency in epithelial ovarian cancer. It is an important mediator of dynein and the development of cancer, owing to its ability to bind to the dynein intermediate light chain (DIC) IC74 and to regulate TGF-beta-dependent transcriptional events. Here we report the 2.1-A crystal structure of Dnlc2A using single anomalous diffraction. The proteins form a homodimer in solution and interact mainly through the helix alpha(2), strand beta(3), and the loop following this strand in each protein to generate a 10-stranded beta-sheet core. The surface of the beta-sheet core is mainly positively charged and predicted (by software PPI-Pred) to be the site that interacts with other partners. At the same time, the residues 79-82, 88, and 90 of each molecule formed two holes in the core. Residue 89 of each molecule, which is crucial for the DIC binding function of Dnlc2A, is within the holes. On the basis of these observations, we propose that the homodimer is the structural and functional unit maintained by hydrogen bonding interactions and hydrophobic packing, and that the patch of the surface of the beta-sheet core is the main area of interaction with other partners. Furthermore, the two holes would be the key sites to interact with IC74.

Binding Sites↗
PubMed2004

Structural stability of oligomeric chaperonin 10: the role of two beta-strands at the N and C termini in structural stabilization.

Chaperonin 10 (cpn10) is a well-conserved subgroup of the molecular chaperone family. GroES, the cpn10 from Escherichia coli, is composed of seven 10kDa subunits, which form a dome-like oligomeric ring structure. From our previous studies, it was found that GroES unfolded completely through a three-state unfolding mechanism involving a partly folded monomer and that this reaction was reversible. In order to study whether these unfolding-refolding characteristics were conserved in other cpn10 proteins, we have examined the structural stabilities of cpn10s from rat mitochondria (RatES) and from hyperthermophilic eubacteria Thermotoga maritima (TmaES), and compared the values to those of GroES. From size-exclusion chromatography experiments in the presence of various concentrations of Gdn-HCl at 25 degrees C, both cpn10s showed unfolding-refolding characteristics similar to those of GroES, i.e. two-stage unfolding reactions that include formation of a partially folded monomer. Although the partially folded monomer of TmaES was considerably more stable compared to GroES and RatES, it was found that the overall stabilities of all three cpn10s were achieved significantly by inter-subunit interactions. We studied this contribution of inter-subunit interactions to overall stability in the GroES heptamer by introducing a mutation that perturbed subunit association, specifically the interaction between the two anti-parallel beta-strands at the N and C termini of this protein. From analyses of the mutants' stabilities, it was revealed that the anti-parallel beta-strands at the subunit interface are crucial for subunit association and stabilization of the heptameric GroES protein.

Amino Acid Sequence↗
PubMed2002

A novel short neurotoxin, cobrotoxin c, from monocellate cobra (Naja kaouthia) venom: isolation and purification, primary and secondary structure determination, and tertiary structure modeling.

A novel short neurotoxin, cobrotoxin c (CBT C) was isolated from the venom of monocellate cobra (Naja kaouthia) using a combination of ion-exchange chromatography and FPLC. Its primary structure was determined by Edman degradation. CBT C is composed of 61 amino acid residues. It differs from cobrotoxin b (CBT B) by only two amino acid substitutions, Thr/Ala11 and Arg/Thr56, which are not located on the functionally important regions by sequence similarity. However, the LD50 is 0.08 mg/g to mice, i.e. approximately five-fold higher than for CBT B. Strikingly, a structure-function relationship analysis suggests the existence of a functionally important domain on the outside of Loop III of CBT C. The functionally important basic residues on the outside of Loop III might have a pairwise interaction with alpha subunit, instead of gamma or delta subunits of the nicotinic acetylcholine receptor (nAChR).

Amino Acid Sequence↗
PubMed2003

Structural basis of adhesion-molecule recognition by ERM proteins revealed by the crystal structure of the radixin-ICAM-2 complex.

ERM (ezrin/radixin/moesin) proteins recognize the cytoplasmic domains of adhesion molecules in the formation of the membrane-associated cytoskeleton. Here we report the crystal structure of the radixin FERM (4.1 and ERM) domain complexed with the ICAM-2 cytoplasmic peptide. The non-polar region of the ICAM-2 peptide contains the RxxTYxVxxA sequence motif to form a beta-strand followed by a short 3(10)-helix. It binds the groove of the phosphotyrosine-binding (PTB)-like subdomain C mediated by a beta-beta association and several side-chain interactions. The binding mode of the ICAM-2 peptide to the FERM domain is distinct from that of the NPxY motif-containing peptide binding to the canonical PTB domain. Mutation analyses based on the crystal structure reveal the determinant elements of recognition and provide the first insights into the physical link between adhesion molecules and ERM proteins.

Amino Acid Sequence↗
PubMed1995

Stability of the WAIS-R and WISC-III factor structure using cross-validation of covariance structures.

The stability of the Verbal Comprehension, Perceptual Organization, and Freedom from Distractibility factors of the WAIS-R and WISC-III was tested using cross-validation of covariance structure models, a methodology that employs unrestricted and restricted factor analyses. Stability was indicated if the goodness of fit of restricted models generated from unrestricted factor patterns did not degrade when applied to other age groups. If goodness of fit degraded inconsistently, the factor structure of one or both instruments was unreliable. If goodness of fit changed in some systematic fashion, an argument for true intellectual changes could be made. Results indicated consistency across age groups. Therefore, it was concluded that the three-factor structure is robust and reliable across age groups and instruments.

Adolescent↗
PubMed2000

Inositolphosphoglycan mediators structurally related to glycosyl phosphatidylinositol anchors: synthesis, structure and biological activity.

The preparation of the pseudopentasaccharide 1a, an inositol-phosphoglycan (IPG) that contains the conserved linear structure of glycosyl phosphatidylinositol anchors (GPI anchors), was carried out by using a highly convergent 2+3-block synthesis approach which involves imidate and sulfoxide glycosylation reactions. The preferred solution conformation of this structure was determined by using NMR spectroscopy and molecular dynamics simulations prior to carrying out quantitative structure--activity relationship studies in connection with the insulin signalling process. The ability of 1a to stimulate lipogenesis in rat adipocytes as well as to inhibit cAMP dependent protein kinase and to activate pyruvate dehydrogenase phosphatase was investigated. Compound 1a did not show any significant activity, which may be taken as a strong indication that the GPI anchors are not the precursors of the IPG mediators.

Animals↗
PubMed1994

Long DNA palindromes, cruciform structures, genetic instability and secondary structure repair.

Long DNA palindromes pose a threat to genome stability. This instability is primarily mediated by slippage on the lagging strand of the replication fork between short directly repeated sequences close to the ends of the palindrome. The role of the palindrome is likely to be the juxtaposition of the directly repeated sequences by intra-strand base-pairing. This intra-strand base-pairing, if present on both strands, results in a cruciform structure. In bacteria, cruciform structures have proved difficult to detect in vivo, suggesting that if they form, they are either not replicated or are destroyed. SbcCD, a recently discovered exonuclease of Escherichia coli, is responsible for preventing the replication of long palindromes. These observations lead to the proposal that cells may have evolved a post-replicative mechanism for the elimination and/or repair of large DNA secondary structures.

Base Sequence↗
PubMed2003

Flexible adaptations in the structure of the tRNA-modifying enzyme tRNA-guanine transglycosylase and their implications for substrate selectivity, reaction mechanism and structure-based drug design.

The enzyme tRNA-guanine transglycosylase (TGT, EC 2.4.2.29) catalyses a base-exchange reaction that leads to anticodon modifications of certain tRNAs. The TGT enzymes of the eubacteria Zymomonas mobilis (Z. mobilis TGT) and Escherichia coli (E. coli TGT) show a different behaviour in the presence of competitive inhibitors. The active sites of both enzymes are identical apart from a single conservative amino acid exchange, namely Tyr106 of Z. mobilis TGT is replaced by a Phe in E. coli TGT. Although Tyr106 is, in contrast to Phe106, hydrogen bonded in the ligand-free structure, we can show by a mutational study of TGT(Y106F) that this is not the reason for the different responses upon competition. The TGT enzymes of various species differ in their substrate selectivity. Depending on the applied pH conditions and/or induced by ligand binding, a peptide-bond flip modulates the recognition properties of the substrate binding site, which changes between donor and acceptor functionality. Furthermore interstitial water molecules play an important role in these adaptations of the pocket. The flip of the peptide bond is further stabilised by a glutamate residue that operates as general acid/base. An active-site aspartate residue, presumed to operate as a nucleophile through covalent bonding during the base-exchange reaction, shows different conformations depending on the nature of the bound ligand. The induced-fit adaptations observed in the various TGT complex structures by multiple crystal-structure analyses are in agreement with the functional properties of the enzyme. In consequence, full understanding of this plasticity can be exploited for drug design.

Aspartic Acid↗
PubMed2003

High-pressure preparation, crystal structure, and properties of alpha-(RE)2B4O9 (RE=Eu, Gd, Tb, Dy): oxoborates displaying a new type of structure with edge-sharing BO4 tetrahedra.

High-pressure/high-temperature conditions of 10 GPa and 1150 degrees C were used to synthesize the new rare-earth oxoborates alpha-(RE)(2)B(4)O(9) (RE=Eu, Gd, Tb, Dy) in a Walker-type multianvil apparatus. Single-crystal X-ray structure determination of alpha-(RE)(2)B(4)O(9) (RE=Eu, Gd, Tb) revealed: C2/c, Z=20, alpha-Eu(2)B(4)O(9): a=2547.9(5), b=444.3(1), c=2493.8(5) pm, beta=99.82(3) degrees, R1=0.0277, wR2=0.0693 (all data); alpha-Gd(2)B(4)O(9): a=2539.0(1), b=443.3(1), c=2490.8(1) pm, beta=99.88(1) degrees, R1=0.0457, wR2=0.0643 (all data); alpha-Tb(2)B(4)O(9): a=2529.4(1), b=441.6(1), c=2484.3(1) pm, beta=99.88(1) degrees, R1=0.0474, wR2=0.0543 (all data). The isotypic compounds exhibit a new type of structure that is built up of BO(4) tetrahedra to form a network that incorporates the rare-earth cations. The most important feature is the existence of the new structural motif of edge-sharing BO(4) tetrahedra next to the known motif of corner-sharing BO(4) tetrahedra, which is realized in the presented compounds alpha-(RE)(2)B(4)O(9) (RE=Eu, Gd, Tb, Dy) for the second time. Furthermore, we report the temperature-resolved in-situ powder-diffraction measurements, DTA, IR/Raman spectroscopic investigations, and magnetic properties of the new compounds.

Journal Article↗
PubMed2004

Fine structures of zeolite-Linde-L (LTL): surface structures, growth unit and defects.

High-resolution electron microscopy (HREM) has been used to image the surface structure of nano- and micrometer-sized synthetic crystals of zeolite-Linde-L (LTL). Columnar holes and rotational, nano-sized, wheel-like defects were observed within the crystals, where the hole has a minimum size equal to that of the rotational defect. Predictions of surface structure from atomistic computer simulation concur with the observations from HREM and provide insight into the crystal growth mechanism of perfect and defective LTL. Analysis of the energetics of the formation of rotational defect structures reveals that the driving force for defect creation is thermodynamic and furthermore, the rotational defects could be created in high concentrations. Formation of a columnar hole is found to be slightly energetically unfavourable and therefore we speculate that the incidence of both rotational and nano-sized vacancy defects is strongly dependent on kinetic factors and reaction conditions. The morphology of nano- and microcrystalline LTL is contradistinct and we use insights from simulation to propose an explanation of the disparity in crystal shape.

Journal Article↗
PubMedDate not supplied

Cytoplasmic tubular structures in liver of HBsAg carrier chimpanzees infected with delta agent and comparison with cytoplasmic structures in non-A, non-B hepatitis.

Electron microscopic observations were carried out on five HBsAg carrier chimpanzees infected with delta (delta) agent and two chimpanzees infected with human non-A, non-B hepatitis. The cytoplasmic tubular structures, which have been recognized in the liver of chimpanzees infected with human non-A, non-B hepatitis, were found also in the liver of HBsAg carrier chimpanzees infected with delta agent. The quantity of the cytoplasmic structures in serial studies was associated with SGPT elevation rather than with expression of delta antigen in sera and liver tissues. This indicates that the cytoplasmic structures reflect a pathologic change of the hepatocytes in chimpanzees infected with delta agent or human non-A, non-B hepatitis. These and other similarities between the two agents suggest a similar nature.

Animals↗
PubMed1987

Three dimensional structure of porcine pancreatic alpha-amylase at 2.9 A resolution. Role of calcium in structure and activity.

The crystal structure of porcine pancreatic alpha-amylase (PPA) has been solved at 2.9 A resolution by X-ray crystallographic methods. The enzyme contains three domains. The larger, in the N-terminal part, consists of 330 amino acid residues. This central domain has the typical parallel-stranded alpha-beta barrel structure (alpha beta)8, already found in a number of other enzymes like triose phosphate isomerase and pyruvate kinase. The C-terminal domain forms a distinct globular unit where the chain folds into an eight-stranded antiparallel beta-barrel. The third domain lies between a beta-strand and a alpha-helix of the central domain, in a position similar to those found for domain B in triose phosphate isomerase and pyruvate kinase. It is essentially composed of antiparallel beta-sheets. The active site is located in a cleft within the N-terminal central domain, at the carboxy-end of the beta-strands of the (alpha beta)8 barrel. Binding of various substrate analogues to the enzyme suggests that the amino acid residues involved in the catalytic reaction are a pair of aspartic acids. A number of other residues surround the substrate and seem to participate in its binding via hydrogen bonds and hydrophobic interactions. The 'essential' calcium ion has been located near the active site region and between two domains, each of them providing two calcium ligands. On the basis of sequence comparisons this calcium binding site is suggested to be a common structural feature of all alpha-amylases. It represents a new type of calcium-protein interaction pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Structural polymorphism of homopurine--homopyrimidine sequences: the secondary DNA structure adopted by a d(GA.CT)22 sequence in the presence of zinc ions.

In this paper, we have analysed the conformational behaviour shown by the homopurine--homopyrimidine alternating d(GA.CT)22 sequence cloned into SV40. Our results show that, in the presence of zinc ions, the d(GA.CT)22 sequence adopts an altered secondary DNA structure (*H-DNA) which differs from either B-DNA or H-DNA. Formation of *H-DNA is facilitated by negative supercoiling and does not appear to require base protonation, since it is induced at neutral pH by approximately 0.4 mM ZnCl2. The patterns of OsO4 and DEPC modification obtained in the presence of zinc are compatible with a homopurine--homopurine--homopyridimine triplex, though other structural models for *H-DNA are also possible. The hypersensitivity to S1-cleavage of the d(GA.CT)22 sequence is reinterpreted in terms of the equilibria between the B-, H- and *H-forms of the sequence. These results reveal the high degree of structural polymorphism shown by homopurine-homopyrimidine sequences. Its biological relevance is discussed.

Animals↗
PubMed2006

Study on blood compatibility with poly(2-methoxyethylacrylate)--relationship between surface structure, water structure, and platelet compatibility in 2-methoxyethylacrylate/2-hydroxyethylmethacrylate diblock copolymer.

Diblock copolymers composed of 2-methoxyethylacrylate (MEA) and 2-hydroxyethylmethacrylate (HEMA) were firstly prepared (the composition ratio = 90/10, 79/21, 66/34, and 48/52 mol/mol) by anion living polymerization. ESCA analysis of their surface structures (dry state) revealed that PMEA segment was segregated to the top surface in all of the polymers, whereas the results of contact angle of water (wet state) showed that the surfaces were covered with PHEMA segment. In vitro platelet adhesion test showed that these polymers had the excellent compatibility with platelet compared to PHEMA homopolymer. Water structure in the hydrated copolymers was investigated by DSC and freezing bound water was observed for all the polymers like PMEA homopolymer, whereas it was not found in PHEMA homopolymer. Further investigation of water structure based on the results of DSC and EWCMS (equilibrium water content by moisture sorption) suggested that freezing bound water existed in PHEMA segment in addition to PMEA segment. We have proposed that the water plays a key role in the appearance of good blood compatibility of the copolymer, according to our previous works (Tanaka et al. Biomacromolecules 2002;3:36-41, Tanaka et al. J Biomed Mater Res A 2004;68:684-695).

Biocompatible Materials↗