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Biomedical subjects

R A Palmer

Publications and source records attributed to R A Palmer.

At least 19 recordsLinked to original sources
PubMed1992

Newly observed binding mode in pancreatic ribonuclease.

Dinucleotides containing guanine, when soaked into crystals of bovine pancreatic ribonuclease, have been found to bind in an unexpected manner, quite unlike interpretations of earlier X-ray diffraction studies. This finding has prompted a reexamination of three mononucleotide-RNase complexes from this laboratory resulting in a re-interpretation of the complex that involved a guanine mononucleotide.

Binding Sites↗
PubMed1991

Novel non-productively bound ribonuclease inhibitor complexes--high resolution X-ray refinement studies on the binding of RNase-A to cytidylyl-2',5'-guanosine (2',5'CpG) and deoxycytidylyl-3',5'-guanosine (3',5'dCpdG).

The X-ray structures of two complexes of bovine ribonuclease-A produced by soaking pre-grown crystals in solutions of the inhibitors cytidylyl-2',5'-guanosine (2',5' CpG) and deoxycytidylyl-3',5'-guanosine (3',5'dCpdG) have been determined at 1.5 A resolution and refined by restrained least squares to R = 21.0% for 17,855 reflections, and R = 19.1% for 16,347 reflections, respectively. Binding of the substrate analogs to the protein has taken place in a completely unexpected and previously unreported manner. In each case the guanine base occupies the well characterized B1 pyrimidine binding site adjacent to Thr-45 (described by Richards, F.M., Wyckoff, H.W., Carlson, W.D., Allewell, N.M., Lee, B. and Mitsui, Y. (1971) Cold Spring Harbor Symp. Quant. Biol. 36, 35-54, and others including Palmer, R.A., Moss, D.S., Haneef, I. and Borkakoti, N. (1984) Biochim. Biophys. Acta 785, 81-88) having entered through a secondary channel external to the active site itself. We designate this reversed non-productive mode as retro-binding. In this mode of binding the SO4(2-) anion bound in the active site of the native protein crystals (Borkakoti, N., Moss, D.S. and Palmer, R.A. (1982) Acta Crystallogr. B38 2210-2217) has not been displaced by the phosphate of the inhibitor molecule as originally anticipated and observed in other studies. Instead the CMP or dCMP moiety of the inhibitor molecule is held loosely in a channel running towards the surface of the protein molecule and is thus completely external to the active site. Consequently, although it has been possible to model them, no attempt has been made to refine either the disordered cytosine in the CpG complex or the deoxycytosine in the dCpdG complex. The traditional B2 purine binding site of RNase (Richards et al., 1971) is unoccupied by the soaked inhibitors. Important changes that have taken place in the protein structure include: stabilization of both Lys-41 and Gln-11 via H-bonding to SO4(2-); stabilization of His-119 in the A conformation (Borkakoti, N., Moss, D.S. and Palmer, R.A. (1982) Acta Crystallogr. B38 2210-2217); and stabilization of SO4(2-) by H-bonds formed with the retro-bound guanine base. Binding of the inhibitors and stabilization of the active site is accompanied by displacement and redistribution of solvent molecules.

Animals↗
PubMed1988

The structure of stiripentol: 4,4 dimethyl- 1-(3,4-methylenedioxyphenyl)-1-penten-3-ol-a novel antiepileptic drug.

C14H18O3, Mr = 234.29, monoclinic, P2(1)/a, a = 14.550 (8), b = 6.133 (4), c = 15.703 (7) A, beta = 116.1 (4) degree, V = 1254.4 (5) A3, Z = 4, Dm = 1.24 (4), Dx = 1.239 g cm-3, lambda (Cu K alpha) = 1.54184 A, mu = 6.15 cm-1, F(000) = 504, room temperature, R = 0.065 for 2426 observed reflections. The five-membered ring A has an envelope conformation, the apical atom C(7)* being out of the plane. The conformation of the side chain attached to C(1)* is almost fully extended. The molecules are packed in a head-to-tail fashion as hydrogen-bonded dimers: O(3)...O(4)* [1-x, y, 1-z] = 3.124 (8), HO(3)...O(4)* = 2.19 (9) A, O(3)-HO(8)...O(4)* V 160.2 (6) degree.

Anticonvulsants↗
PubMed1988

The structure of (1,2-benzisoxazol-3-yl)methanesulfonamide: a novel antiepileptic drug.

C8H8N2O3S, Mr = 212.54, monoclinic, P2(1)/a, a = 7.347 (9), b = 13.237 (4), c = 10.128 (8) A, beta = 108.916 (6) degree, V = 931.9 (1) A3, Z = 4, Dm = 1.52 (4), Dx = 1.514 g cm-3, lambda (Cu K alpha) = 1.54184 A, mu = 28.35 cm-1, F(000) = 440, room temperature, R = 0.040 for 1864 observed reflections. The sulfonamide N forms intermolecular hydrogen bonds with the benzisoxazole ring N and also with the O on the sulfonamide group. Centrosymmetrically related benzisoxazole ring pairs are pi bonded with a high degree of overlap.

Anticonvulsants↗
PubMed1988

Crystallization of mouse pancreatic ribonuclease.

Mouse pancreatic ribonuclease has been crystallized in a form suitable for X-ray structure determination. The crystals grown from solutions of 2-methyl-2,4-pentanediol diffract to high resolution and belong to the hexagonal space group P6(1) (P6(5)) with unit cells dimensions a = b = 64.44 A, c = 53.91 A, y = 120 degrees and V = 1.94 x 10(5) A3 (1 A = 0.1 nm). There are six molecules per unit cell (1 molecule/asymmetric unit), and Vm = 2.3 A3/dalton.

Animals↗
PubMed1987

X-ray refinement study on the binding of cytidylic acid (2'-CMP) to ribonuclease A.

The X-ray structure of the inhibitor complex of bovine ribonuclease A with cytidylic acid (2'-CMP) has been determined at 2.3 A (1 A = 0.1 nm) resolution and refined by restrained least-squares refinement to R = 0.132 for 5650 reflections. Incorporation of the inhibitor molecule has occurred with little disturbance of the protein main-chain atoms, although significant displacement of some side-chain atoms has occurred, particularly in the region of the active site. The binding of 2'-CMP to ribonuclease A is different from that of the related cytidine-N(3)-oxide 2'-phosphate, which has an extra oxygen on N(3) of the cytidine base. The PO4(2-) group is held by hydrogen bond interactions to the side-groups of His 12, Glu 11 and His119. Thr45 is involved in stabilizing the enzyme-ligand complex by forming hydrogen bond interactions between O(gamma) and the pyrimidine base N(3) atom and between the main-chain N(45) and O(2) of the base. Phe120 is much closer to the inhibitor than in the cytidine N(3)-oxide 2'-phosphate structure.

Amino Acid Sequence↗
PubMed1987

Ribonuclease A. Analysis of the hydrogen bond geometry, and spatial accessibility at the active site.

The hydrogen bonding of bovine ribonuclease A derived from the high resolution X-ray structure has been studied in detail. Correlations have been examined for main-chain-main-chain hydrogen bond angles, torsion angles and distances, respectively. Differences are found consistently for correlations associated with alpha-helix and beta-sheet, respectively. Ten of the 124 side-chains have four or more hydrogen bond contacts; two, including Glu-101, have five or more. Three potential C = O---H, three N---X and three potential side-chain H-bonds fail to form. A search for highly inaccessible buried residues resulted in nine outstanding examples, all of which are conserved across 38 known mammalian ribonuclease A sequences, indicating the importance of these residues for structural stability. Of the two histidines in the active site, His-12 has five hydrogen bonds and His-119 three. The conformational space accessible to these two catalytically important residues studied by means of simple non-bonded contact energy calculations confirms the existence of two alternative, interchangeable locations for His-119, while His-12 is locked in a local energy minimum.

Binding Sites↗
PubMed1987

Organizational change in the Medical Library Association: evolution of the continuing education program.

"Change" is a critical dimension of contemporary experience. Library associations are not exempt, and they change in ways similar to other organizations. According to some authorities, four phases typify the process: diagnosis, design, implementation, and incorporation. Focusing on changes in the Medical Library Association's longstanding program of continuing education, the authors utilize the "phase framework" to chart that association's movement from a management system depending primarily upon volunteers to one in which professional staff figure prominently. The historical review serves a heuristic purpose for individuals and institutions in identifying characteristic features of the change process.

Education, Continuing↗
PubMed1986

Accreditation.

Explore the source record for details and available documents.

Accreditation↗
PubMed1985

The antagonism of acetylcholine excitatory and inhibitory responses of Helix central neurones, by some neuromuscular blocking drugs.

Intracellular recordings were made from identified central neurones of the snail Helix aspersa. The antagonism of acetylcholine excitatory and inhibitory responses by d-tubocurarine, HS818 and HS626 was investigated. d-Tubocurarine was equipotent against both the inhibitory and excitatory responses, while HS626 and HS818 were of similar potency to d-tubocurarine in antagonising acetylcholine excitation but were approximately one order of magnitude less potent in antagonising the inhibitory response.

Acetylcholine↗
PubMed1985

Surveillance of nosocomial infections by computer analysis of positive culture rates.

We describe a surveillance method that identifies excessive rates of positive cultures based on patient location, culture site, and organism identification. During a 6-month period, this surveillance method, coupled with epidemiological investigations, identified 19 small clusters of cross-infections and three small outbreaks of intravenous catheter-related bacteremias. These infections were associated with apparent breakdowns in proper technique. Concurrent, standard surveillance activities identified only three of these problems. These results demonstrate that computer analysis of positive culture rates is a sensitive and time-efficient method for detecting potentially preventable nosocomial infections.

Arizona↗
PubMed1979

Use of fracture mechanics theory in lifetime predictions for alumina and bioglass-coated alumina.

The fatigue behavior of alumina and bioglass-coated alumina was determined in air and biological test environments by the dynamic fatigue test technique in which strength is measured as a function of stressing rate. The good correlation found between the test data and fracture mechanics theory indicates that fatigue failure is controlled by the slow crack growth of preexisting flaws and that fracture mechanics theory can be used in making failure predictions for alumina and bioglass-coated alumina in biological environments. Thus, it is believed that lifetime predictions can be made for ceramic implants on the basis of short-term test data utilizing fracture mechanics principles.

Aluminum↗