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Biomedical subjects

R Huber

Publications and source records attributed to R Huber.

At least 649 records · Page 36Linked to original sources
PubMed1976

Dynamics of the aromatic amino acid residues in the globular conformation of the basic pancreatic trypsin inhibitor (BPTI). II. Semi-empirical energy calculations.

The molecular conformation of the basic pancreatic trypsin inhibitor (BPTI) is known in considerable detail from both X-ray studies in single crystals and NMR studies in solution. The NMR experiments showed that the aromatic rings of the phenylalanyl and tyrosyl residues can undergo rapid rotational motions about the C beta--Cv bond. The present paper describes a model investigation of the mechanistic aspects of these intramolecular rotational motions. From calculations of the conformational energies for molecular species derived from the X-ray structure by rotations of individual aromatic rings, it was apparent that the rotational motions of the aromatics could only be understood in a flexible structure. Flexibility was simulated by allowing the protein to relax to an energetically favorable conformation for each of the different rotation states of the aromatic rings. It was then of particular interest to investigate how the perturbations caused by different rotation states of the aromatic rings were propagated in the protein structure. It was found that the rotation axes C beta--Cv were only slightly affected (delta X1 approximately less than 20 degrees. The most sizeable perturbations are caused by through space interactions with nearby atoms, which move away from the ring center and thus release the steric hindrance opposing the rotational motions. The values for the energy barriers obtained from the energy minimization are of the same order of magnitude as those measured by NMR.

Amino Acids↗
PubMed1976

Crystallographic structural studies of a human Fc-fragment. I. An electron-density map at 4 A resolution and a partial model.

The crystal structure of a human Fc fragment was analysed at 4 A resolution. A partial interpretation of the electron-density map in terms of domain structure was possible. The molecule has the shape of a mickey mouse. The spherical domain was interpreted visually and by domain Patterson function interpretation as the CH3 dimer. This dimer resembles closely the CH1-CL dimer found in Fab structures. The ellipsoidal "ears" of the molecule represent the CH2 domains. They are widely separated from each other, but closely connected to CH3. Their tertiary structure must be different from CH1, as Patterson domain interpretations were unsuccessful. A chain tracing in CH2 was not yet possible.

Crystallography↗
PubMed1976

Crystallographic structural studies of a human Fc fragment. II. A complete model based on a Fourier map at 3.5 A resolution.

The crystal structure analysis of a human Fc fragment was pursued to 3.5 A resolution and a complete model was built and refined into the isomorphous Fourier map. The CH2 and CH3 domains show the immunoglobulin fold, with CH3 being closely similar to CH1, but CH2 intermediate in structure between V and CH3. The carbohydrate is rigidly attached to CH2, covering the C face. CH3 dimerizes as CH1-CL, but CH2 has no contact to the second chain. Residues involved in the lateral CH3-CH3 and the longitudinal CH3-CH2 contact are conserved in Ig classes and sub-classes. In IgM and IgE the two C-terminal domains also show this characteristic distribution of contact residues.

Carbohydrates↗
PubMed1976

The frequency of adverse drug reactions as dependent upon age, sex and duration of hospitalization.

In 1972, 171 (18, 7%) of 914 patients showed evidence of an adverse drug reaction (ADR) in a prospective study of the division of internal medicine in a regional teaching hospital (Zieglerspital, Bern). The following factors correlated positively with frequency of ADR: 1. The duration of hospital stay. 2. The age between 60 and 80 years. 3. Female sex. 4. Previous ADR. The fact that most of the ADR occur within the first three weeks of a hospital stay, combined with point 1, suggests early ADR having some predictive value for duration of hospital stay. Statistical data of type, severity, duration and pathogenesis of ADR are given. The drugs involved are mentioned.

Adolescent↗
PubMed1975

The molecular structure of a dimer composed of the variable portions of the Bence-Jones protein REI refined at 2.0-A resolution.

The structure of the variable portions of a K-type Bence-Jones protein REI forming a dimer has been determined by X-ray diffraction to a resolution of 2.0 A. The structure has been refined using a constrained crystallographic refinement procedure. The final R value is 0.24 for 15000 significantly measured reflections; the estimated standard deviation of atomic positions is 0.09 A. A more objective assessment of the error in the atomic positions is possible by comparing the two independently refined monomers. The mean deviation of main-chain atoms of the two chains in internal segments in 0.22 A, of main-chain dihedral angles 6.3 degrees for these segments. The unrefined molecular structure of the VREI dimer has been published (Epp, O., Colman, P., Fehlhammer, H., Bode, W., Schiffer, M., Huber, R., and Palm, W. (1974), Eur. J. Biochem. 45, 513). Now a detailed analysis is presented in terms of hydrogen bonds and conformational angles. Secondary structural elements (antiparallel beta structure, reverse turns) are defined. A more precise atomic arrangement of the amino acid residues forming the contact region and the hapten binding site is given as well as the localization of solvent molecules. Two cis-prolines (Pro-8 and Pro-95) were detected. The intrachain disulfide bridge (Cys-23-Cys-88) occurs statistically in two alternative conformations. The structure suggests reasons for strong conservation of several amino acid residues. The knowledge of the refined molecular structure enables crystal structure analyses of related molecules to be made by Patterson search techniques. The calculated phases based on the refined structure are much improved compared to isomorphous phases. Therefore the effects of hapten binding on the molecular structure can be analyzed by the difference Fourier technique with more reliability. Hapten binding studies have been started.

Amino Acid Sequence↗
PubMed1975

The structure of the complex formed by bovine trypsin and bovine pancreatic trypsin inhibitor III. Structure of the anhydro-trypsin-inhibitor complex.

The structure of the complex between anhydro-trypsin and pancreatic trypsin inhibitor has been determined by difference Fourier techniques using phases obtained from the native complex (Huber et al., 1974). It was refined independently by constrained crystallographic refinement at 1.9 A resolution. The anhydro-complex has Ser 195 converted to dehydro-alanine. There were no other significant structural changes. In particular, the high degree of pyramidalization of the C atom of Lys 15 (I) of the inhibitor component observed in the native complex in maintained in the anhydro-species.

Amino Acids↗
PubMed1975

[Late results of replacement of the antrio-ventricular valve].

From 1966 to 1969 mitral-valve-allografts have been implanted for mitral valve replacement in 11 and for tricuspid valve replacement in two patients. Three patients died immediately after the operation. Eigth allografts in mitral position and one in tricuspid position functioned well. One case was complicated by candida albicans. There were no thromboembolic complications. Long-term follow up revealed late deterioration of allograft function in every case. Four allografts have been replaced four are still functioning four to six years postoperatively. Because of the poor durability of the results this method of mitral valve replacement is not used any more.

Adult↗