Zinc Finger Domain Animation

Zinc fingers are small protein domains that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins or small molecules. The name "zinc finger" was coined to describe the hypothesized structure of the repeated unit in Xenopus laevis transcription factor IIIA.



Classes

Zinc fingers coordinate zinc ions with a combination of cysteine and histidine residues. They can be classified by the type and order of these zinc coordinating residues (e.g. Cys2His2, Cys4, and Cys6). A more systematic method classifies them into different "fold groups" based on the overall shape of the protein backbone in the folded domain. The most common "fold groups" of zinc fingers are the Cys2His2-like (the "classic zinc finger"), treble clef, and zinc ribbon.

Cys2His2

The Cys2His2-like fold group is by far the best characterized class of zinc fingers and are extremely common in mammalian transcription factors. These domains adopt a simple ββα fold and have the amino acid Sequence motif: X2-Cys-X2,4-Cys-X12-His-X3,4,5-His This class of zinc fingers can have a variety of functions such as binding RNA and mediating protein-protein interactions, but is best known for its role in sequence specific DNA-binding proteins such as Zif268. In such proteins, individual zinc finger domains typically occur as tandem repeats with two, three or more fingers comprising the DNA-binding domain of the protein. These tandem arrays can bind in the major groove of DNA and are typically spaced at 3-bp intervals. The α-helix of each domain (often called the "recognition helix") can make sequence specific contacts to DNA bases; residues from a single recognition helix can contact 4 or more bases to yield an overlapping pattern of contacts with adjacent zinc fingers.

Gag knuckle

This fold group is defined by two short β-strands connected by a turn (zinc knuckle) followed by a short helix or loop and resembles the classical Cys2His2 motif with a large portion of the helix and β-hairpin truncated. The best characters members of this family are found in the retroviral nucleocapsid (NC) protein from HIV and other related retroviruses. The gag knuckle zinc finger in the HIV NC protein is the target of a class of drugs known as zinc finger inhibitors.


Treble clef

The treble clef motif consists of a β-hairpin at the N-terminus and an α-helix at the C-terminus that each contribute two ligands for zinc binding, although a loop and a second β-hairpin of varying length and conformation can be present between the N-terminal β-hairpin and the C-terminal α-helix. These fingers are present in a diverse group of proteins that frequently do not share sequence or functional similarity with each other. The best characterized proteins containing treble clef zinc fingers are the [nuclear hormone receptors].

Zn2/Cys6

The canonical members of this class contain a binuclear zinc cluster in which two zinc ions are bound by six cysteine residues. These zinc fingers can be found in several transcription factors including the yeast Gal4 protein.


"Zinc finger." Wikipedia, The Free Encyclopedia. 16 Sep 2009, 10:25 UTC. 16 Sep 2009 <http://en.wikipedia.org/w/index.php?title=Zinc_finger&oldid=314315524>. 

Lysozyme Structure

Lysozymes, also known as muramidase or N-acetylmuramide glycanhydrolase, are a family of enzymes (EC 3.2.1.17) which damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrins. Lysozyme is abundant in a number of secretions, such as tears, saliva, human milk and mucus. It is also present in cytoplasmic granules of the polymorphonuclear neutrophils (PMN). Large amounts of lysozyme can be found in egg white. C-type lysozymes are closely related to alpha-lactalbumin in sequence and structure making them part of the same family.



Function

The enzyme functions by attacking peptidoglycans (found in the cell walls of bacteria, especially Gram-positive bacteria) and hydrolyzing the glycosidic bond that connects N-acetylmuramic acid with the fourth carbon atom of N-acetylglucosamine. It does this by binding to the peptidoglycan molecule in the binding site within the prominent cleft between its two domains. This causes the substrate molecule to adopt a strained conformation similar to that of the transition state[citation needed]. According to Phillips-Mechanism, the lysozyme binds to a hexasaccharide. The lysozyme then distorts the 4th sugar in hexasaccharide (the D ring) into a half-chair conformation. In this stressed state the glycosidic bond is easily broken.

The amino acid side chains glutamic acid 35 (Glu35) and aspartate 52 (Asp52) have been found to be critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, whilst Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule, to give the product of hydrolysis and leaving the enzyme unchanged.

Role in disease
Lysozyme is part of the innate immune system. Children fed infant formula lack lysozyme in their diet and have three times the rate of diarrheal disease. Since lysozyme is a natural form of protection from pathogens like Salmonella, E.coli and Pseudomonas, when it is deficient due to infant formula feeding, can lead to increased incidence of disease.

Whereas the skin is a protective barrier due to its dryness and acidity, the conjunctiva (membrane covering the eye) is instead protected by secreted enzymes, mainly lysozyme and defensin. However, when these protective barriers fail, conjunctivitis results.

PPAR Inhibiors in Cancer Treatment

Poly (ADP-Ribose) Polymerase (PARP) is a protein cells use to repair genetic injuries naturally. But cancer cells also use this protein to repair their own DNA damage. Inhibiting this action allows chemotherapy and radiation to do its job against cancers resulting from genetic mutation.











Alpha Helix

Alpha helix (α-helix) is a right- or left-handed coiled conformation, resembling a spring, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier (i+4 \rightarrow i hydrogen bonding). This secondary structure is also sometimes called a classic Pauling-Corey-Branson alpha helix.


Structure

Geometry and hydrogen bonding

The amino acids in an α helix are arranged in a right-handed helical structure where each amino acid corresponds to a 100° turn in the helix (i.e., the helix has 3.6 residues per turn), and a translation of 1.5 Å (= 0.15 nm) along the helical axis. The pitch of the helix (the vertical distance between two points on the helix) is 5.4 Å (= 0.54 nm)which is the product of 1.5 and 3,6. Most importantly, the N-H group of an amino acid forms a hydrogen bond with the C=O group of the amino acid four residues earlier; this repeated i+4 \rightarrow i hydrogen bonding defines an α-helix. Similar structures include the 310 helix (i+3 \rightarrow i hydrogen bonding) and the π-helix (i+5 \rightarrow i hydrogen bonding). These alternative helices are relatively rare, although the 310 helix is often found at the ends of α-helices, "closing" them off. Transient i+2 \rightarrow i helices (sometimes called δ-helices) have also been reported as intermediates in molecular dynamics simulations of α-helical folding.

Residues in α-helices typically adopt backbone (φ, ψ) dihedral angles around (-60°, -45°). More generally, they adopt dihedral angles such that the ψ dihedral angle of one residue and the φ dihedral angle of the next residue sum to roughly -105°. Consequently, α-helical dihedral angles generally fall on a diagonal stripe on the Ramachandran plot (of slope -1), ranging from (-90°, -15°) to (-35°, -70°). For comparison, the sum of the dihedral angles for a 310 helix is roughly -75°, whereas that for the π-helix is roughly -130°. The general formula for the rotation angle Ω per residue of any polypeptide helix with trans isomers is given by the equation.


The α-helix is tightly packed; there is almost no free space within the helix. The amino-acid side chains are on the outside of the helix, and point roughly "downwards" (i.e., towards the N-terminus), like the branches of an evergreen tree (Christmas tree effect). This directionality is sometimes used in preliminary, low-resolution electron-density maps to determine the direction of the protein backbone.


Stability

Helices observed in proteins can range from four to over forty residues long, but a typical helix contains about ten amino acids (about three turns). Short polypeptides generally do not exhibit much alpha helical structure in solution, since the entropic cost associated with the folding of the polypeptide chain is not compensated for by a sufficient amount of stabilizing interactions. The backbone hydrogen bonds of α-helices are generally considered slightly weaker than those found in β-sheets, and are readily attacked by the ambient water molecules. However, in more hydrophobic environments such as the plasma membrane, or in the presence of co-solvents such as trifluoroethanol (TFE), or isolated from solvent in the gas phase,[6] oligopeptides readily adopt stable α-helical structure.

Photosystem I

Photosystem I is a proteinaceous transmembrane structure composed of several proteins and embedded with pigment molecules. This structure is located inside chloroplasts and secured within the thylakoid membrane with exposure to the thylakoid lumen on one side and to the chloroplast stroma on the other side. PS I acts as an energy converter for various photosynthetic organisms.


Mechanics of Photosystem I

Light energy in the form of photons is converted into electrons to power the generation of ATP or the reduction of NADP+ to NADPH.[4] Photons are received by an antenna complex of pigment molecules. Antenna molecules become photoexcited and pass the energy as resonance energy (text). The resonance energy is transferred to the reaction center pigment chlorophyll a. The reaction center in turn transfers electrons to a primary electron acceptor and subsequent electron acceptors and carriers. Finally, the electrons reduce NADP+ or help generate ATP. Electrons may be recycled to increase the proton concentration in the thylakoid lumen in a process called cyclic electron flow. In cyclic electron flow electrons are passed from the PS I reaction center and then carried to a cytochromeb6f complex where they help transport protons into the thylakoid lumen thus creating ATP.Plastocyanin may accept electrons from the cytochrome b6f complex and pass them along to the reaction center in the antenna complex beginning the cycle again.

F1 component making ATP

Cyclic Photophosphorylation

In cyclic electron flow, the electron begins in a pigment complex called photosystem I, passes from the primary acceptor to plastoquinone, then to cytochrome b6f (a similar complex to that found in mitochondria), and then to plastocyanin before returning to chlorophyll. This transport chain produces a proton-motive force, pumping H+ ions across the membrane; this produces a concentration gradient which can be used to power ATP synthase during chemiosmosis. This pathway is known as cyclic photophosphorylation, and it does not produce O2, as well as ATP. Unlike non-cyclic photophosphorylation, NADP+ does not accept the electrons, but they are sent back to photosystem I. NADPH is NOT produced in cyclic photophosphorylation. In bacterial photosynthesis, a single photosystem is used, and therefore is involved in cyclic photophosphorylation.