Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Crystal structure”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources
PubMed2003

Structural and functional consequences of binding site mutations in transferrin: crystal structures of the Asp63Glu and Arg124Ala mutants of the N-lobe of human transferrin.

Human transferrin is a serum protein whose function is to bind Fe(3+) with very high affinity and transport it to cells, for delivery by receptor-mediated endocytosis. Structurally, the transferrin molecule is folded into two globular lobes, representing its N-terminal and C-terminal halves, with each lobe possessing a high-affinity iron binding site, in a cleft between two domains. Central to function is a highly conserved set of iron ligands, including an aspartate residue (Asp63 in the N-lobe) that also hydrogen bonds between the two domains and an arginine residue (Arg124 in the N-lobe) that binds an iron-bound carbonate ion. To further probe the roles of these residues, we have determined the crystal structures of the D63E and R124A mutants of the N-terminal half-molecule of human transferrin. The structure of the D63E mutant, determined at 1.9 A resolution (R = 0.245, R(free) = 0.261), showed that the carboxyl group still binds to iron despite the larger size of the Glu side chain, with some slight rearrangement of the first turn of alpha-helix residues 63-72, to which it is attached. The structure of the R124A mutant, determined at 2.4 A resolution (R = 0.219, R(free) = 0.288), shows that the loss of the arginine side chain results in a 0.3 A displacement of the carbonate ion, and an accompanying movement of the iron atom. In both mutants, the iron coordination is changed slightly, the principal change being in each case a lengthening of the Fe-N(His249) bond. Both mutants also release iron more readily than the wild type, kinetically and in terms of acid lability of iron binding. We attribute this to more facile protonation of the synergistically bound carbonate ion, in the case of R124A, and to strain resulting from the accommodation of the larger Glu side chain, in the case of D63E. In both cases, the weakened Fe-N(His) bond may also contribute, consistent with protonation of the His ligand being an early intermediate step in iron release, following the protonation of the carbonate ion.

Amino Acid Substitution↗
PubMed2006

Rational design of anticytoadherence inhibitors for Plasmodium falciparum based on the crystal structure of human intercellular adhesion molecule 1.

Adhesion of Plasmodium falciparum-infected erythrocytes (IE) to host endothelium has been associated with pathology in malaria. Although the interaction with endothelial cells can be complex due to the relatively large number of host receptors available for binding, specific proteins have been identified that are more commonly used than others. For example, binding to intercellular adhesion molecule 1 (ICAM 1) is found frequently in parasites from pediatric cases of malaria. The binding site for P. falciparum-infected erythrocytes on ICAM 1 has been mapped in some detail and is distinct from the site for lymphocyte function-associated antigen 1 (LFA-1). Part of the ICAM 1 binding site for P. falciparum-infected erythrocytes (the DE loop) was used to screen a library of compounds based on its structure (derived from the crystal structure of human ICAM 1). This resulted in the identification of 36 structural mimeotopes as potential competitive inhibitors of binding. One of these compounds, (+)-epigalloyl-catechin-gallate [(+)-EGCG], was found to inhibit IE adhesion to ICAM 1 in a dose-dependent manner with two variant ICAM 1-binding parasite lines, providing the first example of a potential mimeotope-based anticytoadherence inhibitor for Plasmodium falciparum.

Animals↗
PubMed1994

Modification of a metal ligand in carbonic anhydrase: crystal structure of His94-->Glu human isozyme II.

One of the zinc ligands in human carbonic anhydrase II, His94, has been replaced with glutamic acid by site-directed mutagenesis. The mutation leads to a less stable zinc binding site and to significant non-local perturbations of the protein structure. The crystals are composed of a mixture of holo- and apoenzyme, and the side chain of Glu94 has two conformations. In the holoenzyme, Glu94 coordinates to the metal ion and is hydrogen bonded to Gln92. In the apo form, Glu94 is hydrogen bonded to Asn67. The mutation has resulted in a 500-fold decrease of the catalyzed rate of CO2 hydration (kcat/Km).

Apoenzymes↗
PubMed1998

Conformations of kinesin: solution vs. crystal structures and interactions with microtubules.

Recently, the molecular structures of monomeric and dimeric kinesin constructs in complex with ADP have been determined by X-ray crystallography (Kull et al. 1996; Kozielski et al. 1997 a; Sack et al. 1997). The "motor" or "head" domains have almost identical conformations in the known crystal structures, yet the kinesin dimer is asymmetric: the orientation of the two heads relative to the coiled-coil formed by their neck regions is different. We used small angle solution scattering of kinesin constructs and microtubules decorated with kinesin in order to find out whether these crystal structures are of relevance for kinesin's structure under natural conditions and for its interaction with microtubules. Our preliminary results indicate that the crystal structures of monomeric and dimeric kinesin are similar to their structures in solution, though in solution the center-of-mass distance between the motor domains of the dimer could be slightly greater. The crystal structure of dimeric kinesin can be interpreted as representing two equivalent conformations. Transitions between these or very similar conformational states may occur in solution. Binding of kinesin to microtubules has conformational effects on both, the kinesin and the microtubule. Solution scattering of kinesin decorated microtubules reveals a peak in intensity that is characteristic for the B-surface lattice and that can be used to monitor the axial repeat of the microtubules under various conditions. In decoration experiments, dimeric kinesin dissociates, at least partly, leading to a stoichiometry of 1:1 (one kinesin head per tubulin dimer; Thormählen et al. 1998a) in contrast to the stoichiometry of 2:1 reported for dimeric ncd. This discrepancy is possibly due to the effect of steric hindrance between kinesin dimers on adjacent binding sites.

Animals↗
PubMed2006

Probing the electronic structure of platinum(II) chromophores: crystal structures, NMR structures, and photophysical properties of six new bis- and di- phenolate/thiolate Pt(II)diimine chromophores.

A general route for synthesis of six structurally similar Pt(II) diimine thiolate/phenolates chromophores possessing bulky phenolate or thiolate ligands is reported. The Pt chromophores were characterized using an array of techniques including 1H, 13C, and 195Pt NMR, absorption, emission, (spectro)electrochemistry, and EPR spectroscopy. Systematic variation of the electronic structure of the Pt(II) chromophores studied was achieved by (i) changing solvent polarity; (ii) substituting oxygen for sulfur in the donor ligand; (iii) alternating donor ligands from bis- to di-coordination; and (iv) changing the electron donating/withdrawing properties of the ligand(s). The lowest excited state in these new chromophores was assigned to a [charge-transfer-to-diimine] transition from the HOMO of mixed Pt/S (or Pt/O) character on the basis of absorption and emission spectroscopy, UV/vis (spectro)electrochemistry, and EPR spectroscopy. One of the chromophores, Pt(dpphen)(3,5-di-tert-butyl-catecholate) represents an example of a Pt(II) diimine phenolate chromophore that possesses a reversible oxidation centered predominantly on the donor ligand. Results from EPR spectroscopy indicate participation of the Pt(II) orbitals in the HOMO. There is a dramatic difference in the photophysical properties of carborane complexes compared to other mixed-ligand Pt(II) compounds, which includes room-temperature emission and photostability. The charge-transfer character of the lowest excited state in this series of chromophores is maintained throughout. Moreover, the absorption and emission energies and the redox properties of the excited state can be significantly tuned.

Crystallization↗
PubMed2003

Crystal structures of ferrous horse heart myoglobin complexed with nitric oxide and nitrosoethane.

The interactions of nitric oxide (NO) and organic nitroso compounds with heme proteins are biologically important, and adduct formation between NO-containing compounds and myoglobin (Mb) have served as prototypical systems for studies of these interactions. We have prepared crystals of horse heart (hh) MbNO from nitrosylation of aqua-metMb crystals, and we have determined the crystal structure of hh MbNO at a resolution of 1.9 A. The Fe-N-O angle of 147 degrees in hh MbNO is larger than the corresponding 112 degrees angle previously determined from the crystal structure of sperm whale MbNO (Brucker et al., Proteins 1998;30:352-356) but is similar to the 150 degrees angle determined from a MS XAFS study of a frozen solution of hh MbNO (Rich et al., J Am Chem Soc 1998;120:10827-10836). The Fe-N(O) bond length of 2.0 A (this work) is longer than the 1.75 A distance determined from the XAFS study and suggests distal pocket influences on FeNO geometry. The nitrosyl N atom is located 3.0 A from the imidazole N(epsilon) atom of the distal His64 residue, suggesting electrostatic stabilization of the FeNO moiety by His64. The crystal structure of the nitrosoethane adduct of ferrous hh Mb was determined at a resolution of 1.7 A. The nitroso O atom of the EtNO ligand is located 2.7 A from the imidazole N(epsilon) atom of His64, suggesting a hydrogen bond interaction between these groups. To the best of our knowledge, the crystal structure of hh Mb(EtNO) is the first such determination of a nitrosoalkane adduct of a heme protein.

Animals↗
PubMed1995

Analysis of local helix bending in crystal structures of DNA oligonucleotides and DNA-protein complexes.

Sequence-dependent bending of the helical axes in 112 oligonucleotide duplex crystal structures resident in the Nucleic Acid Database have been analyzed and compared with the use of bending dials, a computer graphics tool. Our analysis includes structures of both A and B forms of DNA and considers both uncomplexed forms of the double helix as well as those bound to drugs and proteins. The patterns in bending preferences in the crystal structures are analyzed by base pair steps, and emerging trends are noted. Analysis of the 66 B-form structures in the Nucleic Acid Database indicates that uniform trends within all pyrimidine-purine and purine-pyrimidine steps are not necessarily observed but are found particularly at CG and GC steps of dodecamers. The results support the idea that AA steps are relatively straight and that larger roll bends occur at or near the junctions of these A-tracts with their flanking sequences. The data on 16 available crystal structures of protein-DNA complexes indicate that the majority of the DNA bends induced via protein binding are sharp localized kinks. The analysis of the 30 available A-form DNA structures indicates that these structures are also bent and show a definitive preference for bending into the deep major groove over the shallow minor groove.

Base Sequence↗
PubMed2001

Structures of furanosides: geometrical analysis of low-temperature X-ray and neutron crystal structures of five crystalline methyl pentofuranosides.

Crystal structures of all five crystalline methyl D-pentofuranosides, methyl alpha-D-arabinofuranoside (1), methyl beta-D-arabinofuranoside (2), methyl alpha-D-lyxofuranoside (3), methyl beta-D-ribofuranoside (4) and methyl alpha-D-xylofuranoside (5) have been determined by means of cryogenic X-ray and neutron crystallography. The neutron diffraction experiments provide accurate, unbiased H-atom positions which are especially important because of the critical role of hydrogen bonding in these systems. This paper summarizes the geometrical and conformational parameters of the structures of all five crystalline methyl pentofuranosides, several of them reported here for the first time. The methyl pentofuranoside structures are compared with the structures of the five crystalline methyl hexopyranosides for which accurate X-ray and neutron structures have been determined. Unlike the methyl hexopyranosides, which crystallize exclusively in the C(1) chair conformation, the five crystalline methyl pentofuranosides represent a very wide range of ring conformations.

Journal Article↗
PubMed2006

Crystal structure and physical properties of two polymorphs of ropivacaine HCl.

The crystal structure of two polymorphs of ropivacaine HCl have been determined, as well as their relative stability up to 100 degrees C. A geometric restriction for a solid-state transition between the two polymorphs has been identified. The packing density along the H-bonded chains form the basis for a model explaining the kinetic crystallization of the metastable form. The difference in stability and physicochemical properties between the two polymorphs can be attributed to the difference in crystal structure.

2-Propanol↗
PubMed1998

Rice non-specific lipid transfer protein: the 1.6 A crystal structure in the unliganded state reveals a small hydrophobic cavity.

This study describes the high-resolution X-ray structure of the non-specific lipid transfer protein (ns-LTP) from rice seeds in the unliganded state. The model has been refined to a crystallographic R-factor of 0.186 for 8.0 to 1.6 A data (with Fo > 2 sigma F). It accounts for all 91 amino acid residues, 68 water molecules, one sulfate ion, and two molecules of 3-[cyclohexylamino]-1-propanesulfonic acid. The root-mean-square deviations from ideal bond lengths and angles are 0.017 A and 1.76 degrees, respectively. The overall fold of rice ns-LTP is very similar to that of maize ns-LTP. A superposition of 91 common C alpha atoms in rice and maize ns-LTPs, both in the unliganded state, gives a root-mean-square deviation of 1.2 A. Large structural differences from the crystal structure of maize ns-LTP are observed in two regions: the loop between two alpha-helices H1 and H2, where one residue deletion (Gln21 of maize sequence) occurs, and the C-terminal region around Tyr79. The C-terminal region of rice protein is somewhat collapsed into the hydrophobic cavity. As a consequence, its hydrophobic cavity is considerably smaller than that of maize protein (144 A3 versus 408 A3 for van der Waals cavity volumes), despite a high level of sequence identity (79%) between them. In the rice ns-LTP structure, the side-chain of Arg44 partially blocks the mouth of the cavity, while the side-chain of Ile81 effectively closes the other end by protruding into the cavity. And the side-chain of Tyr79 divides the cavity into two parts, with the larger part being shielded from the solvent. The present study illuminates the structure-function relationship of rice ns-LTP and allows a detailed structural comparison with other plant ns-LTPs.

Amino Acid Sequence↗
PubMed1998

A structural basis for transition-state stabilization in antibody-catalyzed hydrolysis: crystal structures of an abzyme at 1. 8 A resolution.

The three-dimensional structure of a catalytic antibody, 6D9, has been solved as a complex with a transition state analog. The structure was determined from two different crystal forms, and was refined at a resolution of 1.8 A. The antibody 6D9, which was induced by immunization with the phosphonate transition state analog 3, hydrolyzes a prodrug of chloramphenicol monoester 1 to generate the parent drug 2. The kinetic studies have shown that the antibody is catalytic by virtue of the theoretical relationship between the affinity for the transition state and the catalytic efficiency (kcat/kuncat=KS/KTSA). The crystal structure makes it possible to visualize the theoretical relationship. A side-chain (Nepsilon) of HisL27D is placed in a key position to make a hydrogen bond to the phosphonate oxygen of the transition state analog with a distance of 2.72 A, suggesting a hydrogen bond to the oxyanion developing in the transition state of the hydrolysis. There are no catalytic residues, other than the histidine, around the phosphonate moiety. In addition, in the antibody-hapten complex, the hapten bears a folded conformation and the two stacked aromatic rings are buried deep in the antigen-combining site through aromatic-aromatic interaction with TrpH100I and TyrH58. The conformation of the bound hapten suggests that the antibody binds the substrate to change the conformation of the ester moiety to a thermodynamically unstable E-form, thereby making it easy for the substrate to reach the transition-state during catalysis. These observations reveal that the catalytic mechanism is explained purely on the basis of the stabilization of the transition state. The refined high resolution structures reported here are envisaged to have an impact on the understanding of other hydrolytic antibodies, since their haptens share some unique features with the hapten used in this study.

Antibodies, Catalytic↗
PubMed1990

The crystal structure and thermotropic liquid-crystal properties of N-n-undecyl-D-gluconamide.

N-n-Undecyl-D-gluconamide, C17H35O6, crystallizes in space group P1, with one molecule in a unit cell a = 5.2267(6), b = 19.628(9), c = 4.7810(4) A, alpha = 93.23(2), beta = 95.60(1), gamma = 89.58(2) degrees, V = 487.35 A3, Dx = 1.19 g.cm-3. The crystal lattice is isostructural with N-n-heptyl-D-gluconamide having monolayer head-to-tail molecular packing. The molecules have a V-shaped conformation. The hydrogen bonding of the gluconamide moieties includes a four-link homodromic cycle. The transition to a smectic A liquid-crystal phase at 156.7 degrees is preceded by two crystal-to-crystal phase transitions at 77.2 degrees and 99.4 degrees. The long d-spacing of the intermediate crystal phase of 39 A, and the d-spacing of the liquid-crystal phase of 32 A, are consistent with a transition to a bilayer head-to-head molecular packing.

Carbohydrate Conformation↗
PubMed2003

Structure-based drug design: synthesis, crystal structure, biological evaluation and docking studies of mono- and bis-benzo[b]oxepines as non-steroidal estrogens.

Mono- and bis-benzo[b]oxepine derivatives have been rationally synthesized to meet the molecular requirement for interaction with estrogen receptor. Bis-benzo[b]oxepines (7 and 9) and mono-benzo[b]oxepine (10) acquire geometry with phenolic groups disposed in a fashion to stimulate estrogen receptor. Structure-based investigation, in vivo activity and docking studies have been described and correlated to demonstrate a practical approach for suitable ligand design.

Drug Design↗