Biomedical subjects

D Himmel

Publications and source records attributed to D Himmel.

16 recordsLinked to original sources

PubMed1999

Atomic structure of scallop myosin subfragment S1 complexed with MgADP: a novel conformation of the myosin head.

The crystal structure of a proteolytic subfragment from scallop striated muscle myosin, complexed with MgADP, has been solved at 2.5 A resolution and reveals an unusual conformation of the myosin head. The converter and the lever arm are in very different positions from those in either the pre-power stroke or near-rigor state structures; moreover, in contrast to these structures, the SH1 helix is seen to be unwound. Here we compare the overall organization of the myosin head in these three states and show how the conformation of three flexible "joints" produces rearrangements of the four major subdomains in the myosin head with different bound nucleotides. We believe that this novel structure represents one of the prehydrolysis ("ATP") states of the contractile cycle in which the myosin heads stay detached from actin.

Adenosine Diphosphate↗

PubMed1988

Interaction of tetrandrine with slowly inactivating calcium channels. Characterization of calcium channel modulation by an alkaloid of Chinese medicinal herb origin.

Tetrandrine, a bis-benzylisoquinoline alkaloid derived from the Chinese medicinal herb Stephania tetrandra, is a putative Ca2+ entry blocker whose mechanism of action is unknown. To investigate this mechanism, the effects of tetrandrine were characterized on binding of three chemical classes of Ca2+ entry blockers in cardiac sarcolemmal membrane vesicles. In the range 25-37 degrees C, tetrandrine completely blocks diltiazem binding, partially inhibits D-600 binding, and markedly stimulates nitrendipine binding, with greatest enhancement occurring at 37 degrees C. The potency of tetrandrine is increased 10-fold as temperature is raised from 25 to 37 degrees C. Scatchard analyses indicate that inhibition of diltiazem binding and stimulation of nitrendipine binding result from changes in ligand affinities while inhibition of D-600 binding is due to both an increase in KD and decrease in Bmax of aralkylamine receptors. Ligand dissociation studies reveal that tetrandrine increases D-600 off-rates, decreases nitrendipine off-rates, but has no effect on diltiazem dissociation kinetics. In addition, tetrandrine reversibly blocks inward Ca2+ currents through L-type Ca2+ channels in GH3 anterior pituitary cells. These results indicate that tetrandrine interacts directly at the benzothiazepine-binding site of the Ca2+ entry blocker receptor complex and allosterically modulates ligand binding at other receptors in this complex. These findings suggest that tetrandrine is a structurally unique natural product Ca2+ entry blocker and provide a rationale explanation for the therapeutic effectiveness of this agent.

Alkaloids↗

PubMed1987

[Status of ultrasound and roentgen diagnosis in prenatal detection of osteochondrodysplasias].

Ultrasound and X-ray investigation have a specific but complementary importance within the prenatal recording of lethal osteochondrodysplasia. In the prenatal diagnoses of thanatophoric dysplasia, asphyxiating thoracic dysplasia, chondrodysplasia punctata and achondroplasia we present our procedure for the investigation. All pregnant women are examined by ultrasound. Where the sonographical findings--according to our previous definition for the above mentioned diseases--suggest that they may be present we recommend referral to an institution with highly-specialized diagnostic possibilities for further investigation. Already in the II. trimester of pregnancy it is possible to make such group diagnoses by ultrasound. To give further specificity to the findings prenatal X-ray investigation should be done preferably in the III. trimester. The importance of confirming the diagnosis by either postnatal or postmortem X-ray investigation should be emphasized.

Adult↗

PubMed1986