Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The crystal structure of a class A beta-lactamase from Staphylococcus aureus PC1 has been refined at 2.0 A resolution. The resulting crystallographic R-factor (R = sigma h parallel Fo[-]Fc parallel/sigma h[Fo], where [Fo] and [Fc] are the observed and calculated structure factor amplitudes, respectively), is 0.163 for the 17,547 reflections with I greater than or equal to 2 sigma (I) within the 8.0 A to 2.0 A resolution range. The molecule consists of two closely associated domains. One domain is formed by a five-stranded antiparallel beta-sheet with three helices packing against a face of the sheet. The second domain is formed mostly by helices that pack against the second face of the sheet. The active site is located in the interface between the two domains, and many of the residues that form it are conserved in all known sequences of class A beta-lactamases. Similar to the serine proteases, an oxyanion hole is implicated in catalysis. It is formed by two main-chain nitrogen atoms, that of the catalytic seryl residue, Ser70, and that of Gln237 on an edge beta-strand of the major beta-sheet. Ser70 is interacting with another conserved seryl residue, Ser130, located between the two ammonium groups of the functionally important lysine residues, Lys73 and Lys234. Such intricate interactions point to a possible catalytic role for this second seryl residue. Another key catalytic residue is Glu166. There are several unusual structural features associated with the active site. (1) A cis peptide bond has been identified between the catalytic Glu166 and Ile167. (2) Ala69 and Leu220 have strained phi, psi dihedral angles making close contacts that restrict the conformation of the active site beta-strand involved in the formation of the oxyanion hole. (3) A buried aspartate residue, the conserved Asp233, is located next to the active site Lys234. It is interacting with another buried aspartyl residue, Asp246. An internal solvent molecule is also involved, but the rest of its interactions with the protein indicate it is not a cation. (4) Another conserved aspartyl residue that is desolvated is Asp131, adjacent to Ser130. Its charge is stabilized by interactions with four main-chain nitrogen atoms. (5) An internal cavity underneath the active site depression is filled with six solvent molecules. This, and an adjacent cavity occupied by three solvent molecules partially separate the omega-loop associated with the active site from the rest of the protein.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Biol 1991 Feb 20
PMID:Refined crystal structure of beta-lactamase from Staphylococcus aureus PC1 at 2.0 A resolution. 200 20

The tendency of mammalian sperm-egg fusion to occur at a site away from the first polar body was investigated in a homologous (mouse oocytes and mouse spermatozoa) and in a heterologous model (hamster oocytes and mouse spermatozoa). Following micromanipulation of the zona pellucida either in proximity to or opposite the first polar body, in vitro fertilization was performed and subsequent differences in sperm-egg interaction were evaluated. Since spermatozoa from random-bred mice do not readily penetrate intact zonae pellucidae in vitro, it is likely that zona penetration occurred through the artificial holes in both models. The creation of a gap in the zona pellucida opposite the first polar body was associated with levels of sperm fusion that were significantly higher than those resulting from manipulation near the first polar body. Spermatozoa were rarely found to penetrate the hole completely, and in general few spermatozoa were observed in the pervitelline space. The proximity between pronuclei following sperm penetration was correlated with the position of the incision with respect to the polar body. The findings suggest that breaching the zona pellucida for microsurgical fertilization should be performed away from the microvillus-free area of the oocyte.
Mol Reprod Dev 1991 Feb
PMID:A preferential site for sperm-egg fusion in mammals. 200 32

Crystals of proaerolysin, the precursor of the hole-forming toxin from Aeromonas hydrophila, have been obtained. The mature form of this protein binds to a receptor on mammalian cells, aggregates and forms 30 A holes in the membrane. The crystals are tetragonal, space group P4(3)2(1)2, a = b = 104.00 A, c = 222.0 A. They contain a dimer in the asymmetric unit and diffract to a resolution of 2.6 A.
J Mol Biol 1990 Apr 20
PMID:Crystallization of a proform of aerolysin, a hole-forming toxin from Aeromonas hydrophila. 232 76

Horseradish peroxidase (HRP) injected into one lateral geniculate nucleus of male inbred PVG/Mol hooded rats is taken up by terminals of the optic nerve and transported retrogradely towards the opposite retina. Four hours after injection when a small portion of HRP had reached the retina, the eye and optic nerve were excised and incubated in vitro at 38 degrees C for another 3.5 hr during which the intraocular pressure (IOP) was set at 30 or 0 mmHg. During the in vitro period additional HRP entered the retina by axonal transport if the incubation medium contained enough Ca2+. Transport occurred at 0.45-1.1 mM Ca2+, but not at 0.30mM Ca2+. When transport occurred, no significant difference in degree of transport was found between the two pressures. The amount of HRP transported at 30 and 0 mmHg was very similar to that at 20 mmHg but significantly higher than that at 50 mmHg, (values at 20 and 50 mmHg from an earlier study). Thus, fast retrograde HRP transport was equally efficient at or near a physiological IOP as at zero pressure. Also, the degree of transport inhibition was not proportional to the height of the IOP, but started to increase above 30 mmHg. This is probably due to the presence of supporting tissue in the optic nerve head and inherent strength of the nerve fibers themselves. The lamina cribrosa in the rat eye is poorly developed and a shearing force on the nerve fibers due to laminar hole misalignment can largely be excluded. Effects on blood circulation are also excluded by the in vitro situation.
 ...
PMID:Influence of low IOP and low calcium on retrograde axoplasmic transport in rat optic nerve in vitro. 242 Jun 29

Proteins of either HIV-1, hepatitis B, or rabies virus were incorporated with the adjuvant substance Quil A and cholesterol into the immunostimulating complex: iscom. Formation and symmetry of this regular complex were analyzed by electron microscopy. Micellar structures with a diameter of about 12 nm, occasionally with a 7-nm stain-filled center, were formed in a 0.03% water suspension of Quil A. Cavities or holes appeared in the smooth structures of cholesterol upon the addition of Quil A, and after mixing Quil A and cholesterol 1:1 fragile and flattened structures of matrix were produced with a diameter of about 40 nm. By freeze-drying the matrix was preserved as a cage-like, isometric particle. Stable iscom particles composed of Quil A, cholesterol, and selected viral proteins had an approximate diameter of 32 nm. The particles had an uniform, cage-like structure, exhibiting icosahedral symmetry, irrespective of the viral proteins incorporated. Tilting experiments and rotational image analysis indicated that the iscoms were composed of 20 morphological subunits assembled in a pentagonal dodecahedron with a hole on each of the 12 pentagonal faces. The symmetrical shape of the iscom might explain both its remarkable stability and its capacity to efficiently present antigens to the immune system.
J Ultrastruct Mol Struct Res 1989 Dec
PMID:Quaternary structure of the immunostimulating complex (iscom). 263 9

Three-dimensional image reconstruction has been applied to electron micrographs of noncrystalline, negatively stained ribosomes obtained from Escherichia coli. Several independent reconstructions all show an overall appearance resembling models that had been derived earlier by direct visual interpretation of electron micrographs. The reconstructed ribosomes show numerous structural details not recognized previously, some of which may be functionally significant. A large elongate cavity (approximately 8-nm long x 5-nm wide x 6-nm [maximal] deep) is present on the surface of the ribosome near the base of its stalk and is identifiable as a portion of a feature termed the interface canyon, which was detected in prior reconstructions of the large ribosomal subunit (Radermacher, M., T. Wagenknecht, A. Verschoor, and J. Frank. 1987. EMBO (Eur. Mol. Biol. Organ.) J. 6:1107-1114). On the back of the ribosome, near the base of the central protuberance, is a hole leading to the interface canyon, which likely represents an exit site for the elongating polypeptide produced during protein biosynthesis. The exposed portion of the interface canyon appears well suited to bind two tRNA molecules in a configuration that is consistent with biochemical and structural data on the mechanism of peptide bond biosynthesis.
 ...
PMID:Three-dimensional reconstruction of the ribosome from Escherichia coli. 264 63

The crystal structure of porcine cytosolic adenylate kinase has been established at 2.1 A resolution using a restrained least-squares refinement method. Based on 11,251 independent reflections of better than 10 A resolution, a final R-factor of 19.3% was obtained with a model obeying standard geometry within 0.026 A in bond lengths and 3.3 degrees in bond angles. In comparison with the previous structure at 3 A resolution, there is a significant improvement. The high resolution structure has been used to rationalize the strictly conserved residues in the adenylate kinase family. Among these is the glycine-rich loop, which forms a giant anion hole accommodating a sulfate ion which mimics a phosphoryl group of a substrate. Such a structure seems to occur in a large group of mononucleotide binding proteins. Moreover, a conserved cis-proline has been detected in the active center. A structural comparison with the complex between adenylate kinase from yeast and a substrate-analog at medium resolution indicates that this kinase performs appreciable mechanical movements during a catalytic cycle. The reported structure presumably represents an open form of the enzyme, similar to that in solution in the absence of substrates. However, since there are large intermolecular contacts in the crystal, some deviation from the solution structure has to be expected.
J Mol Biol 1988 Jan 20
PMID:Refined structure of porcine cytosolic adenylate kinase at 2.1 A resolution. 283 12

A latent multifunctional protease with a molecular weight of 722,000 to 760,000 purified from rat liver cytosol has been reported. This paper reports on the structure and subunit composition of the enzyme. Electron microscopy showed that the enzyme was a ring-shaped particle of 160(+/- 7) A diameter and 110(+/- 10) A height with a small hole of 10 to 30 A diameter (1 A = 0.1 nm). Small-angle X-ray scattering analysis indicated that the enzyme had a prolate ellipsoidal structure with an ellipsoid cavity in the center. The maximum dimension of the enzyme was estimated to be 210 A from a pair-distance distribution function. The radius of gyration obtained from a Guinier plot and the Stokes radius based on the ellipsoidal model were 66 A and 76 A, respectively. On two-dimensional gel electrophoresis, the purified enzyme separated into 13 to 15 characteristic components with molecular weights of 22,000 to 33,000 and isoelectric points of 4 to 9. These multiple components were not artifacts produced by limited proteolysis during purification of the enzyme, because the cell-free translation products in a reticulocyte lysate with poly(A)-mRNA of rat liver consisted of multiple components of similar sizes, and because peptide mapping analyses with lysylendopeptidase and V8 protease demonstrated clear differences in the primary structures of these components. The 13 main components were isolated from the purified enzyme by reverse-phase high performance liquid chromatography and shown to be non-identical. A model of the enzyme is proposed on the basis of these observations and previous physicochemical studies. Interestingly, the morphology of this protease is similar to that of the 16 to 22 S ring-shaped particles found in a variety of eukaryotic organisms. The structural similarity between this multi-protease complex and various reported subcellular particles is discussed.
J Mol Biol 1988 Oct 20
PMID:Molecular organization of a high molecular weight multi-protease complex from rat liver. 306 84

The three-dimensional reconstruction of the connector of bacteriophage phi 29 has been obtained from tilt series of negatively stained tetragonal ordered aggregates under low-dose conditions and up to a resolution of (1/1.8) nm-1. These connectors are built up as dodecamers of only one structural polypeptide (p10). Two connectors form the crystal unit cell, each one facing in the opposite direction with respect to the plane of the crystal and partially overlapping. The main features of the two connectors that build the unit cell were essentially the same, although they were negatively stained in slightly different ways, probably due to their situations with respect to the carbon-coated support grid. The main features of the phi 29 connector structure revealed by this three-dimensional reconstruction are: the existence of two clearly defined domains, one with a diameter of around 14 nm and the other narrower (diameter approximately equal to 7.5 nm); an inner hole running all along the structure (around 7 to 8 nm in height) with a cylindrical profile and an average diameter of 4 nm; a general 6-fold symmetry along the whole structure and a 12-fold one in the wider domain; a clockwise twist of the more contrasted regions of both domains from the narrower towards the wider domain (the direction of DNA encapsidation). These features are compatible with an active role for the connector in the process of DNA packaging.
J Mol Biol 1986 Dec 20
PMID:Three-dimensional reconstruction of the connector of bacteriophage phi 29 at 1.8 nm resolution. 358 12

The structure of the connector of bacteriophage T3 (built up by the product of gene 8) has been studied in two dimensions by combined use of translational and rotational image filtering procedures applied to tetragonal ordered aggregates of the former oligomers. This analysis, performed up to 1/1.6 nm-1 resolution, has revealed the existence of a 12-fold symmetry in the outermost region of the specimen (mainly between radii 5.2 and 6.7 nm), a 6-fold one in the inner region (between radii 1.7 and 3.2 nm), and a hole in its center. These features are very similar to the ones described for the connectors of other phages, such as T4, lambda, and phi 29, thus suggesting a common mechanism for the functions carried out by this viral region.
J Ultrastruct Mol Struct Res 1986 Feb
PMID:Bacteriophage T3 gene 8 product oligomer structure. 378 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>