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C Sander

Publications and source records attributed to C Sander.

At least 181 records · Page 10Linked to original sources
PubMed1991

Detection of common three-dimensional substructures in proteins.

We present a fully automatic algorithm for three-dimensional alignment of protein structures and for the detection of common substructures and structural repeats. Given two proteins, the algorithm first identifies all pairs of structurally similar fragments and subsequently clusters into larger units pairs of fragments that are compatible in three dimensions. The detection of similar substructures is independent of insertion/deletion penalties and can be chosen to be independent of the topology of loop connections and to allow for reversal of chain direction. Using distance geometry filters and other approximations, the algorithm, implemented in the WHAT IF program, is so fast that structural comparison of a single protein with the entire database of known protein structures can be performed routinely on a workstation. The method reproduces known non-trivial superpositions such as plastocyanin on azurin. In addition, we report surprising structural similarity between ubiquitin and a (2Fe-2S) ferredoxin.

Algorithms↗
PubMed1991

The structure of ColE1 rop in solution.

The structure of the ColE1 repressor of primer (rop) protein in solution was determined from the proton nuclear magnetic resonance data by a combined use of distance geometry and restrained molecular dynamics calculations. A set of structures was determined with low internal energy and virtually no violations of the experimental distance restraints. Rop forms homodimers: Two helical hairpins are arranged as an antiparallel four helix bundle with a left-handed rope-like twist of the helix axes and with left-handed bundle topology. The very compact packing of the side chains in the helix interfaces of the rop coiled-coil structure may well account for its high stability. Overall, the solution structure is highly similar to the recently determined X-ray structure (Banner, D.W., Kokkinidis, M. and Tsernoglou, D. (1987) J. Mol. Biol., 196, 657-675), although there are minor differences in regions where packing forces appear to influence the crystal structure.

Bacterial Proteins↗
PubMed1991

The role of heat-shock and chaperone proteins in protein folding: possible molecular mechanisms.

Recently some heat-shock proteins have been linked to functions of 'chaperoning' protein folding in vivo. Here current experimental evidence is reviewed and possible requirements for such an activity are discussed. It is proposed that one mode of chaperone action is to actively unfold misfolded or badly aggregated proteins to a conformation from which they could refold spontaneously; that improperly folded proteins are recognized by excessive stretches of solvent-exposed backbone, rather than by exposed hydrophobic patches; and that the molecular mechanism for unfolding is either repeated binding and dissociation ('plucking') or translocation of the protein backbone through a binding cleft ('threading'), allowing the threaded chain to refold spontaneously. The observed hydrolysis of ATP would provide the energy for active unfolding. These hypotheses can be applied to both monomeric folding and oligomeric assembly and are sufficiently detailed to be open to directed experimental verification.

Heat-Shock Proteins↗
PubMed1991

Interactions between megakaryocytes and sinus wall. An ultrastructural study on bone marrow tissue in primary (essential) thrombocythemia.

An ultrastructural study was performed on bone marrow tissue in primary (essential) thrombocythemia to evaluate possible interactions between megakaryocytes and sinusoids. In addition to a preferential localization of megakaryocytes in the subendothelial space, two different kinds of cytoplasmic processes could be discriminated penetrating the sinus wall. Serial sections disclosed that megakaryocytes developed multiple pseudopod-like plump projections derived from their peripheral zone and devoid of organelles. It is tempting to speculate that these ameboid features could serve as anchors to keep the cell in a subendothelial position and to monitor changes occurring in circulation. The second type of cytoplasmic processes reaching into the vascular lumen consisted of tentacle-like elongated protrusions rich in organelles, apparently originating from the intermediate zone. These projections were thought to present either the beginning of megakaryocytes egress into circulation or putative platelets. Frequently, there was an intrasinusoidal localization of megakaryocytes which revealed numerous so-called platelet territories and apparently an enforced platelet shedding. Generally, these features are comparable with aspects obtained from animal studies, following excessively stimulated megakaryo- and thrombocytopoiesis by application of anti-platelet serum.

Bone Marrow↗
PubMed1991

Ultrastructure of bone marrow tissue in so-called primary (idiopathic) myelofibrosis-osteomyelosclerosis (agnogenic myeloid metaplasia). II. The myeloid stroma (hematopoietic microenvironment).

An ultrastructural study was performed on bone marrow tissue in 8 patients revealing early and late stages of so-called primary (idiopathic) myelofibrosis - osteomyelosclerosis (agnogenic myeloid metaplasia) to evaluate the constituents of the hematopoietic microenvironment (myeloid stroma). A survey of the stroma cells disclosed an overall increase, particularly in so-called undifferentiated (primitive - pluripotent), but also in transitional (fibroblastic) reticular cells and myofibroblasts. The most primitive reticular cells were characterized by their stellate aspect with elongated slender cytoplasmic processes traversing the interstitial space, and by the scarcity of organelles. The transition into a fibroblast was preceded by the appearance of branching cisternal structures of the rough endoplasmic reticulum, extensively developed Golgi fields and an abundance in mitochondria. Frequently, so-called myofibroblasts were encountered displaying bundles of filaments along the subplasmalemmal region. Extracellularly fibrillar material with an irregular cross-banding as well as microfibrils could be observed. The many vascular structures (sinusoids and capillaries) exhibited a multilayered basement membrane-like material including many fibrils and adventitial cells (pericytes, smooth muscle and transitional reticular cells) with numerous cytoplasmic processes. Undifferentiated and transitional reticular cells as well as myofibroblasts seem to form an integral part of the hematopoietic microenvironment in OMF and are assumed to play an important role for the evolution of the disease-specific myelofibrosis in this disorder.

Bone Marrow↗
PubMed1991

Ultrastructure of bone marrow tissue in so-called primary (idiopathic) myelofibrosis-osteomyelosclerosis (agnogenic myeloid metaplasia). I. Abnormalities of megakaryopoiesis and thrombocytes.

An electron microscopic study was conducted with the aim to analyze abnormalities of the megakaryopoiesis in bone marrow tissue of patients suffering from so-called primary (idiopathic) myelofibrosis-osteomyelosclerosis. In comparison with control specimens and in confirmation of light microscopical findings, a pronounced pleomorphism of the megakaryocytic cell line could be observed consisting of giant forms, micromegakaryocytes and naked (pyknotic) nuclei. Further atypias were expressed by a dissociation of nuclear-cytoplasmic maturation. These included particularly the amount of dense granules, and the development of the demarcation membrane system as well as the occurrence of emperipolesis (i.e. internalization of hematopoietic cells) already in immature or megakaryoblastic elements. In these specimens there was a striking variety in the appearance of dense granules of the alpha or bull's eye type revealing frequent elongated roll- and dumbbell-like shapes and a doubling of the nucleoids. Thrombocytes showed giant forms with either hypertrophy of the open canalicular system or abundance of dense granules and beta-glycogen accumulation. Remarkable was a focal sponge-like proliferation of the open canalicular system in many of the large platelets and giant and fused granules of the alpha and osmiophilic type. The abnormalities disclosed in megakaryo- and thrombocytes may have certain functional implications, i.e. to hemorrhage and thrombosis which are often encountered out of proportion to the platelet counts in this disorder. Moreover, those anomalies indicate a disorganization of megakaryopoiesis which may contribute to the abnormal release of factors (platelet-derived growth factor and factor 4) predominantly involved in the process of myelofibrosis.

Blood Platelets↗
PubMed1990

Proton nuclear magnetic resonance assignments and secondary structure determination of the ColE1 rop (rom) protein.

The complete resonance assignment of the ColE1 rop (rom) protein at pH 2.3 was obtained by two-dimensional (2D) proton nuclear magnetic resonance spectroscopy (1H NMR) at 500 and 600 MHz using through-bond and through-space connectivities. Sequential assignments and elements of regular secondary structure were deduced by analysis of nuclear Overhauser enhancement spectroscopy (NOESY) experiments and 3JHN alpha coupling constants. One 7.2-kDa monomer of the homodimer consists of two antiparallel helices connected by a hairpin loop at residue 31. The C-terminal peptide consisting of amino acids 59-63 shows no stable conformation. The dimer forms a four-helix bundle with opposite polarization of neighboring elements in agreement with the X-ray structure.

Amino Acid Sequence↗
PubMed1990

Immunohistochemical localization of rhodanese.

The role of rhodanese in the detoxication of acute cyanide exposure is controversial. The debate involves questions of the availability of rhodanese to cyanide in the peripheral circulation. Blood-borne cyanide will distribute to the brain and may induce lesions or even death. The present study addresses the dispute by determining the distribution of rhodanese in tissues considered to have the highest rhodanese activity and thought to serve as major detoxication sites. The results indicate that rhodanese levels are highest in (1) hepatocytes that are in close proximity to the blood supply of the liver (2) epithelial cells surrounding the bronchioles (a major entry route for gaseous cyanide) and (3) proximal tubule cells of the kidney (serving to facilitate cyanide detoxication and elimination as thiocyanate). Rhodanese activity in the brain is low compared with liver and kidney (Mimori et al., 1984; Drawbaugh & Marrs, 1987); the brain is not considered to be a major site of cyanide detoxication. The brain, however, is the target for cyanide toxicity. In this study our goal was also to differentiate the distribution of rhodanese in an area of the brain. We found that the enzyme level is highest in fibrous astrocytes of the white matter. Cyanide-induced brain lesions may thus occur in areas of the brain lacking sufficient sites for detoxication.

Animals↗
PubMed1990

Excluded volume approximation to protein-solvent interaction. The solvent contact model.

Important properties of globular proteins, such as the stability of its folded state, depend sensitively on interactions with solvent molecules. Existing methods for estimating these interactions, such as the geometrical surface model, are either physically misleading or too time consuming to be applied routinely in energy calculations. As an alternative, we derive here a simple model for the interactions between protein atoms and solvent atoms in the first hydration layer, the solvent contact model, based on the conservation of the total number of atomic contacts, a consequence of the excluded-volume effect. The model has the conceptual advantage that protein-protein contacts and protein-solvent contacts are treated in the same language and the technical advantage that the solvent term becomes a particularly simple function of interatomic distances. The model allows rapid calculation of any physical property that depends only on the number and type of protein-solvent nearest-neighbor contacts. We propose use of the method in the calculation of protein solvation energies, conformational energy calculations, and molecular dynamics simulations.

Amino Acids↗
PubMed1990

Molecular cloning of YPT1/SEC4-related cDNAs from an epithelial cell line.

Molecular analysis of Saccharomyces cerevisiae secretion mutants has led to the identification of two Ras-like GTP-binding proteins, Ypt1p and Sec4p, which are essential for transport along the exocytic route. To study the regulation of membrane traffic in epithelial cells, a set of 11 clones encoding proteins similar to the YPT1/SEC4 products were isolated from an MDCK (Madin-Darby canine kidney) cell cDNA library. Four of these proteins, Rab8, -9, -10, and -11, are novel members of this subfamily of Ras-like proteins, and two of them are closely related to Ypt1p and Sec4p. The ratio of the number of clones isolated over the total number screened reveals a high level of complexity for this subfamily of GTP-binding proteins. This diversity supports their proposed function in controlling different steps in membrane traffic.

Amino Acid Sequence↗
PubMed1990

[Fine structure of megakaryocyte precursor cells (promegakaryoblasts) derived from smears and sections of bone marrow tissue in patients with chronic myeloid leukemia and so-called primary osteomyelofibrosis with accompanying thrombocythemia].

An immunomorphometric study (antiglycoprotein III a - Y2/51) was performed on routinely processed trephine biopsies in 24 patients with chronic myeloid leukemia (CML) as well as so-called primary osteomyelofibrosis (OMF) to determine the frequency and fine structure of promegakaryoblasts (PMB). With respect to controls, there was a significant increase in megakaryocytes in both entities with an orderly expansion of the precursor subpopulation in CML, but a relative decrease in OMF. In comparison with smears of aspirates, sizes of PMB were reduced by about 25% (factor 1.4) in the corresponding bone marrow sections.

Bone Marrow↗
PubMed1990

[Advantages of biplane transesophageal echocardiography].

Biplane transesophageal echocardiography (BTEE) was intraoperatively performed on 27 patients; ten patients with coronary artery bypass graft surgery, ten with aortic valve replacement, five with mitral valve replacement, one with reconstruction of complete AV-canal, and one with surgical repair of dissecting aortic aneurysm. Compared with the transverse views of the monoplane TEE, BTEE permits the following additional images of the heart: 1) Longitudinal "two-chamber-view" for assessment of left ventricular (LV) anterior, apical, and posterior wall motion, and for assessment of mitral valve anatomy and function (e.g., grading of color flow regurgitation). 2) Imaging of the right-ventricular outflow tract (RVOT) for evaluation of RVOT obstruction, including a crosswise imaging of aortic valve. 3) Proximal two-thirds of the aorta ascendens for the diagnosis of dissecting aortic aneurysm (de Bakey Types I and II). 4) Imaging of the superior vena cava, helpful for detecting transposition of pulmonary veins. 5) Apex of left ventricle, advantageous for detecting thrombus. 6) Longitudinal view of the descending aorta: from the origin of the left subclavian artery down to the origin of the coeliac artery (origins of both vessels, inclusively). We prepared post mortem sections of the heart corresponding to the longitudinal echocardiographic views and documented them by photography. In conclusion, the second plane provides an important improvement in semi-invasive imaging of the heart.

Adult↗
PubMed1989

Thermitase, a thermostable subtilisin: comparison of predicted and experimental structures and the molecular cause of thermostability.

The subtilisin family of proteases has four members of known sequence and structure: subtilisin Carlsberg, subtilisin novo, proteinase K, and thermitase. Using thermitase as a test case, we ask two questions. How good are methods for model building a three-dimensional structure of a protein based on sequence homology to a known structure? And what are the molecular causes of thermostability? First, we compare predicted models of thermitase, refined by energy minimization and varied by molecular dynamics, with the preliminary crystal structure. The predictions work best in the conserved structural core and less well in seven loop regions involving insertions and deletions relative to subtilisin. Here, variation of loop regions by molecular dynamics simulation in vacuo followed by energy minimization does not improve the prediction since we find no correlation between in vacuo energy and correctness of structure when comparing local energy minima. Second, in order to identify the molecular cause of thermostability we confront hypotheses derived by calculation of the details of interatomic interactions and estimates of hydrophobic interactions with inactivation experiments. As a result, we can exclude salt bridges and hydrophobic interactions as main causes of thermostability. Based on a combination of theoretical and experimental evidence, the unusually tight binding of calcium by thermitase emerges as the most likely single influence responsible for its increased thermostability.

Actinomycetales↗
PubMed1989

What's new in human herpesvirus-6? Clinical immunopathology of the HHV-6 infection.

Human herpesvirus-6 (HHV-6), formerly known as human B-lymphotropic virus (HBLV), was first isolated in 1986 from patients with lymphoproliferative disorders and AIDS. Antibody prevalence against HHV-6 varies between about 60-80% indicating a widespread latent infection. Although HHV-6 infects in vivo primarily T-lymphocytes, it is associated with similar diseases as in infection with Epstein-Barr virus (EBV), a clearly B-lymphotropic virus. Reactivation of latent HHV-6 infection in patients with subnormal host defense may cause persistent active infection with so-called postinfectious chronic fatigue syndrome (PICFS) or may contribute to other pathologies such as immune deficiency itself, autoimmune disorders or progressive lymphoproliferation. Coinfection of CD4 cells by HHV-6 and human immunodeficiency virus (HIV 1) in AIDS patients can aggravate HIV-induced acquired immune deficiency. These characteristics of the only recently detected new virus justify further intense investigation.

Herpesviridae Infections↗
PubMed1989

Histologic examination of the placenta in the growth-retarded fetus.

This investigation was undertaken to determine whether histologic examination of the placenta contributed to a better understanding of the cause of intrauterine fetal growth retardation. Placentas were examined of 151 liveborn infants whose birthweights were in the lower 10th percentile for gestational age. One or more histologic aberrations were found in 139 (92%) cases, in contrast to one or more antenatal risk factors (primarily hypertension) in 77 (51%) cases or a gross placental abnormality (primarily abruption) in 46 (30%) cases. Compared with placentas belonging to appropriately sized fetuses, histologic signs of uteroplacental vascular insufficiency, chronic inflammation, and hemorrhagic endovasculitis were significantly more common in the study group. The primary histologic condition was supportive of prior clinical impressions in 61 (40%) cases, contradictory in 23 (15%) cases, or solely contributory to explaining the growth retardation in 55 (36%) cases. Placental histologic examination may clarify a cause for delayed fetal growth, especially after a normotensive pregnancy.

Female↗
PubMed1989

Polarity as a criterion in protein design.

Hypothetical proteins can be tested computationally by determining whether or not the designed sequence-structure pair has the characteristics of a typical globular protein. We have developed such a test by deriving quantities with approximately constant value for all globular proteins, based on empirical analysis of the exposed and buried surfaces of 128 structurally known proteins. The characteristic quantities that best appear to segregate badly designed or deliberately misfolded proteins from their properly folded natural relatives are the polar fraction of side chains on the protein surface and, independently, in the protein interior. Three of the seven hypothetical structures tested here can be rejected as having too many polar side-chain groups in the interior or too few on the protein surface. In addition, a recently designed nutritional protein is identified as being very much unlike globular proteins. These database-derived characteristic quantities are useful in screening designed proteins prior to experiment and may be useful in screening experimentally determined (X-ray, NMR) protein structures for possible errors.

Electric Conductivity↗
PubMed1989

Conservation of residue interactions in a family of Ca-binding proteins.

In the TNC family of Ca-binding proteins (calmodulin, parvalbumin, intestinal calcium binding protein and troponin C) approximately 70 well-conserved amino acid sequences and six crystal structures are known. We find a clear correlation between residue contacts in the structures and residue conservation in the sequences: residues with strong sidechain-sidechain contacts in the three-dimenesional structure tend to be the more conserved in the sequence. This is one way to quantify the intuitive notion of the importance of sidechain interactions for maintaining protein three-dimensional structure in evolution and may usefully be taken into account in planning point mutations in protein engineering.

Amino Acid Sequence↗