Disulfide location

Muta, T., Hashimoto, R., Miyata, T., Nishimura, H., Toh, Y., and Iwanaga, S., 1990, Proclotting enzyme from horseshoe crab hemocytes. cDNA cloning, disulfide locations, and subcellular localization. /. Biol. Chem. 265 22426-22433. 

The earliest method for manufacturiag carbon disulfide involved synthesis from the elements by reaction of sulfur and carbon as hardwood charcoal in externally heated retorts. Safety concerns, short Hves of the retorts, and low production capacities led to the development of an electric furnace process, also based on reaction of sulfur and charcoal. The commercial use of hydrocarbons as the source of carbon was developed in the 1950s, and it was still the predominate process worldwide in 1991. That route, using methane and sulfur as the feedstock, provides high capacity in an economical, continuous unit. Retort and electric furnace processes are stiU used in locations where methane is unavailable or where small plants are economically viable, for example in certain parts of Africa, China, India, Russia, Eastern Europe, South America, and the Middle East. Other technologies for synthesis of carbon disulfide have been advocated, but none has reached commercial significance. 

Disulfide bridges formation ChEs contain 8-10 cysteines six of these form three internal disulfide bridges. The cysteine that is located four amino acids upstream the carboxyl terminus forms a disulfide bridge with a cysteine of an identical subunit, creating an interchain disulfide bridge, which stabilizes the dimeric structure. 

The primary structure - the sequence of peptide-bonded amino acids in the protein chain and the location of any disulfide bridges. 

Figure 48-3. Schematic representation of fibronectin. Seven functional domains of fibronectin are represented two different types of domain for heparin, cell-binding, and fibrin are shown. The domains are composed of various combinations of three structural motifs (I, II, and III), not depicted in the figure. Also not shown is the fact that fibronectin is a dimer joined by disulfide bridges near the carboxyl terminals of the monomers. The approximate location of the RGD sequence of fibronectin, which interacts with a variety of fibronectin integrin receptors on cell surfaces, is indicated by the arrow. (Redrawn after Yamada KM Adhesive recognition sequences.

Biocatalysis refers to catalysis by enzymes. The enzyme may be introduced into the reaction in a purified isolated form or as a whole-cell micro-organism. Enzymes are highly complex proteins, typically made up of 100 to 400 amino acid units. The catalytic properties of an enzyme depend on the actual sequence of amino acids, which also determines its three-dimensional structure. In this respect the location of cysteine groups is particularly important since these form stable disulfide linkages, which hold the structure in place. This three-dimensional structure, whilst not directly involved in the catalysis, plays an important role by holding the active site or sites on the enzyme in the correct orientation to act as a catalyst. Some important aspects of enzyme catalysis, relevant to green chemistry, are summarized in Table 4.3. 

The reaction of metallic copper with thiuram disulfides yields complexes of Cu I), which are polymeric in solution as well as in the solid state 121,122). In 123) the copper atoms are located at the corners of a slightly distorted tetrahedron with Cu—Cu distances ranging from 2.6—2.7 A. Each of the copper atoms is coordinated to three sulfur atoms in a nearly planar triangular arrangement and each sulfur atom coordinates one or two copper atoms. 

No studies were located regarding interactions with other substances in humans or animals after exposure to diisopropyl methylphosphonate. However, the potential for multiple chemical interactions does exist. Diisopropyl methylphosphonate has been identified in the RMA in the presence of many other chemicals (such as endrin, dieldrin, dicyclopentadiene, bicycloheptdiene, diethyl benzene, and diethyl disulfide). The nervous system is a target of many of these compounds found at the RMA, including diisopropyl methylphosphonate. Therefore, there is potential for interaction, and studies examining multiple exposures would be useful in predicting risk to humans. Workers at the RMA reported skin irritation after dermal exposure to diisopropyl methylphosphonate at concentrations around 11.3 ppm in water. However, several other chemicals were also in the area (NIOSH 1981). Therefore, it is not clear if diisopropyl methylphosphonate contributed to the effects. 

The essential distinction between the approaches used to formulate and evaluate proteins, compared with conventional low molecular weight drugs, lies in the need to maintain several levels of protein structure and the unique chemical and physical properties that these higher-order structures convey. Proteins are condensation polymers of amino acids, joined by peptide bonds. The levels of protein architecture are typically described in terms of the four orders of structure [23,24] depicted in Fig. 2. The primary structure refers to the sequence of amino acids and the location of any disulfide bonds. Secondary structure is derived from the steric relations of amino acid residues that are close to one another. The alpha-helix and beta-pleated sheet are examples of periodic secondary structure. Tertiary... 

Most of the G-protein-coupled receptors are homologous with rhodopsin however, other quantitatively minor families as well as some individual receptors do not share any of the structural features common to the rhodopsin family (Figure 2.3). The most dominant of these are the glucagon/VIP/caldtonin receptor family, or family B (which has approximately 65 members), and the metabotropic glutamate receptor family, or family C (which has approximately 15 members), as well as the frizzled/smoothened family of receptors. Thus, the only structural feature that all G-protein-coupled receptors have in common is the seven-transmembrane helical bundle. Nevertheless, most non-rhodopsin-like receptors do have certain minor structural features in common with the rhodopsin-like receptors — for example, a disulfide bridge between the top of TM-III and the middle of extracellular loop-3, and a cluster of basic residues located just below TM-VI. 

Structural and functional evidence clearly demonstrates that family C receptors function as dimers, either as homodimers or as heterodimers. The metabotropic glutamate receptors and the calcium sensors, as discussed in Section 2.6.1, are found as covalently connected dimers in which there is a disulfide bridge between a Cys residue located in a loop in the N-terminal extracellular domain of each monomer. This disulfide bridge apparently serves only to hold the monomers in close proximity, as the loop is so unstructured that it does not resolve in the x-ray structure. 

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