Wednesday, December 8, 2010

Möbius fold ? Human apolipoprotein A-I

The structure of truncated human apolipoprotein A-I (PDB code 1AV1) is the major protein component of high density lipoprotein. High-density lipoprotein (HDL) is one of the five major groups of lipoproteins which, in order of sizes, largest to smallest, are chylomicrons, VLDL, IDL, LDL and HDL, which enable lipids like cholesterol and triglycerides to be transported within the blood stream.
The molecule consists almost entirely of a pseudo-continuous, amphipathic alpha-helix that is punctuated by kinks at regularly spaced proline residues; it adopts a shape similar to a horseshoe of dimensions 12.5 x 8.0 x 4.0 nanometers. Four molecules in the asymmetric unitassociate via their hydrophobic faces to form an antiparallel four-helix bundle with an elliptical ring shape.

Friday, October 15, 2010

Platelet activating factor - T0297

This is 2HSJ, a putative platelet activating factor from Streptococcus pneumonia (The causative agent of pneumonia). To me this is T0297, a target from the CASP7 protein structure prediction contest and has since been on eof my pet proteins for studying folding and prediction.

Tuesday, June 29, 2010

Tudor domain

The double tudor domain is part of the human Lysine-specific demethylase 4A and recognizes the methylation state of histones. Histones are proteins found in the nucleus of cells where they organize the DNA by wrapping it around them selves. They are intimately involved in the regulation of gene expression through their methylation state. This proteins allows the cells to "sense" the methylation and is part of Lysine-specific demethylase 4A which is able to remove the methylation from histones allowing them to bind to DNA again. This would switch of any genes in the affected stretch of DNA.

Monday, June 21, 2010

7-bladed propeller fold

Amongst the most intruiging protein folds, the propeller fold comes in a number of varieties. Shown here is a 7 bladed version, but they occur in 3 to 8 bladed varieties. Note that this fold is constructed from a single chain, rather than from 7 identical units, although this fold almost certainly arose from internal duplications of gene segments. Many hundreds of protein structures with this fold have been determined. In the case of enzymes the enzyme's active site is often found in the cleft formed in the center of the propeller by loops connecting the successive four-sheet motifs. Examples include the the influenza virus protein neuraminidase - one of two proteins present in the viral envelope. It catalyzes the cleavage of sialic acid moieties from cell-membrane proteins to aid in the targeting of newly produced virions to previously uninfected cells.

"peptide self-assembly mimic" (PSAM) scaffold

PSAMs are engineered water-soluble proteins that mimic a segment of beta-rich peptide self-assembly, and they are amenable to standard biophysical techniques and systematic mutagenesis. The PSAM beta-sheet contains rows of repetitive amino acid patterns running perpendicular to the strands (cross-strand ladders) that represent a ubiquitous structural feature of fibril-like surfaces. These engineered proteins are study systems for understanding degenerative amyloid diseases such as Alzheimer's or Creuzfeld-Jacob disease.

Thursday, June 10, 2010

DNA Gyrase

DNA Gyrase from E.Coli is an enzyme belonging to the class of Topoisomerases, which allows the organism to modify the topology of its DNA. In other words it helps untangle, un-knot and relax supercoils in its DNA genome. It does so by binding to a strand of DNA, cutting both strands and then, while keeping hold of both cut ends, passing another piece of double stranded DNA through the gap. It then reseals the double stranded break. Essentially it allows portions of the large circular bacterial genome to pass through itself, such as to prevent knotting and entanglement. A number of antibiotics (e.g. Simocyclinone D8) target this enzyme, since it is essential to the organism's survival. Humans also have a form of this enzyme but it's construction is different and we are thus not affected by the antibiotics.

Tuesday, June 8, 2010

Insulin hexamer

Insulin is produced by the Islets of Langerhans in the Pancreas of mammals and induces liver and muscle cells to take up glucos (typically after a meal) from the blood. Shown here is a hexameric form, coordinated by two zinc ions, believed to be the form in which it is stored in the beta-cells of the islets of Langerhans prior to release. Inability to produce insulin (forvarious reasons) leads to the common disease of diabetes.

Hydroperoxide resistance protein OsmC (1vla)

Apoptosome-Procaspase-9 - CARD Complex

Neurotrophin (Nerve growth factor (NGF))

NGF is a signaling molecule that binds to sympathetic and sensory neuron surfaces and prevents them from going into apoptosis (cell death). It is part of a larger family of signaling proteins collectively knows as neurotrophins. NGF has been shown to play a role in disorders as varied as coronary atherosclerosis, obesity, type 2 diabetes, and metabolic syndrome.

Human liver alcohol dehydrogenase.

Alcohol dehydrogenase (ADH) is found in the human liver and is part of a group of seven dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of NAD+ to NADH. In humans and many other animals, they serve to break down alcohols which could otherwise be toxic, including ethanol.