Chymotrypsin is a digestive enzyme component of pancreatic juice acting in the duodenum, where it performs proteolysis, the breakdown of proteins and polypeptides. Chymotrypsin preferentially cleaves peptide amide bonds where the side chain of the amino acid N-terminal to the scissile amide bond is a large hydrophobic amino acid; these amino acids contain an aromatic ring in their side chain that fits into a hydrophobic pocket of the enzyme. It is activated in the presence of trypsin; the hydrophobic and shape complementarity between the peptide substrate P1 side chain and the enzyme S1 binding cavity accounts for the substrate specificity of this enzyme. Chymotrypsin hydrolyzes other amide bonds in peptides at slower rates those containing leucine and methionine at the P1 position. Structurally, it is the archetypal structure for the PA clan of proteases. Chymotrypsin is synthesized in the pancreas by protein biosynthesis as a precursor called chymotrypsinogen, enzymatically inactive. Trypsin activates chymotrypsinogen by cleaving peptidic bonds in positions Arg15 - Ile16 and produces π-chymotrypsin.

In turn, aminic group of the Ile16 residue interacts with the side chain of Glu194, producing the "oxyanion hole" and the hydrophobic "S1 pocket". Moreover, chymotrypsin induces its own activation by cleaving in positions 14-15, 146-147, 148-149, producing α-chymotrypsin; the resulting molecule is a three-polypeptide molecule interconnected via disulfide bonds. In vivo, chymotrypsin is a proteolytic enzyme acting in the digestive systems of many organisms, it facilitates the cleavage of peptide bonds by a hydrolysis reaction, which despite being thermodynamically favorable, occurs slowly in the absence of a catalyst. The main substrates of chymotrypsin are peptide bonds in which the amino acid N-terminal to the bond is a tryptophan, phenylalanine, or leucine. Like many proteases, chymotrypsin hydrolyses amide bonds in vitro, a virtue that enabled the use of substrate analogs such as N-acetyl-L-phenylalanine p-nitrophenyl amide for enzyme assays. Chymotrypsin cleaves peptide bonds by attacking the unreactive carbonyl group with a powerful nucleophile, the serine 195 residue located in the active site of the enzyme, which becomes covalently bonded to the substrate, forming an enzyme-substrate intermediate.

Along with histidine 57 and aspartic acid 102, this serine residue constitutes the catalytic triad of the active site. These findings rely on inhibition assays and the study of the kinetics of cleavage of the aforementioned substrate, exploiting the fact that the enzyme-substrate intermediate p-nitrophenolate has a yellow colour, enabling measurement of its concentration by measuring light absorbance at 410 nm; the reaction of chymotrypsin with its substrate was found to take place in two stages, an initial “burst” phase at the beginning of the reaction and a steady-state phase following Michaelis-Menten kinetics. The mode of action of chymotrypsin explains this. First, acylation of the substrate to form an acyl-enzyme intermediate, deacylation to return the enzyme to its original state; this occurs via the concerted action of the three-amino-acid residues in the catalytic triad. Aspartate hydrogen bonds to the N-δ hydrogen of histidine, increasing the pKa of its ε nitrogen, thus making it able to deprotonate serine.

This deprotonation allows the serine side chain to act as a nucleophile and bind to the electron-deficient carbonyl carbon of the protein main chain. Ionization of the carbonyl oxygen is stabilized by formation of two hydrogen bonds to adjacent main chain N-hydrogens; this occurs in the oxyanion hole. This forms a tetrahedral breakage of the peptide bond. An acyl-enzyme intermediate, bound to the serine, is formed, the newly formed amino terminus of the cleaved protein can dissociate. In the second reaction step, a water molecule is activated by the basic histidine, acts as a nucleophile; the oxygen of water attacks the carbonyl carbon of the serine-bound acyl group, resulting in formation of a second tetrahedral adduct, regeneration of the serine -OH group, release of a proton, as well as the protein fragment with the newly formed carboxyl terminus Trypsin PA clan of proteases The MEROPS online database for peptidases and their inhibitors: S01.001 Chymotrypsin at the US National Library of Medicine Medical Subject Headings

1995 Masters (snooker)

The 1995 Benson & Hedges Masters was a professional non-ranking snooker tournament that took place between 5 and 12 February 1995 at the Wembley Conference Centre in London, England. The wild-card players were John Higgins, who had won the 1994 Grand Prix, Mark Williams, who won the 1994 Benson & Hedges Championship. Both of them were 19 years old. Higgins went on to reach the final. Ronnie O'Sullivan defeated Higgins 9–3 in the final to become the youngest Masters champion aged 19 years and 69 days; this still remains a record. Stephen Hendry meanwhile failed to make the final for the first time in his Masters career, losing to Peter Ebdon 3–5 in the quarter-finals. Defending champion Alan McManus was the number 1 seed with World Champion Stephen Hendry seeded 2. Places were allocated to the top 16 players in the world rankings. Players seeded 15 and 16 played in the wild-card round against the winner of the qualifying event, Mark Williams, John Higgins, the wild-card selection. Tony Drago, John Higgins, Joe Swail and Mark Williams were making their debuts in the Masters.

In the preliminary round the wild-card players played the 15th and 16th seeds: Mark Williams won the qualifying tournament, known as the 1994 Benson & Hedges Championship at the time. Total: 13 141, 112 Stephen Hendry 132 Tony Drago 131, 129, 103 Peter Ebdon 125 Terry Griffiths 111, 106, 104 John Higgins 104 Darren Morgan 104 Alan McManus 102 Ronnie O'SullivanTony Drago's century and John Higgins's 106 were scored in the wild-card round

Gibson Melody Maker

The Gibson Melody Maker is an electric guitar made by Gibson Guitar Corporation. It has had many body shape variations since its conception in 1959; the Gibson Melody Maker was first launched in 1959 and discontinued in 1971. It had a one-piece mahogany neck. All the electronics, from the small single-coil pickups to the cable jack, were assembled on the pickguard and installed in a rout in the front of the body; the strings ran from a straight-sided simplification of the traditional Gibson headstock at one end to a wraparound bridge/tailpiece unit at the other. From 1959 until 1961, the Melody Maker had a single cutaway slab body style similar to the early Les Paul Junior model but thinner. In 1961 the body style changed to a symmetrical double cutaway, resembling a Gretsch 6122 or a Danelectro Shorthorn; the body style was changed in 1966 to a style similar to the SG, with pointed "horns", a large white scratchplate, white pickup covers instead of black. Note: Melody Maker "D" refers to the double pickup model of any vintage but is mistakenly used for the double cutaway model.

Options on the Melody Maker included the "D" model and a short-scale 3/4 neck. In 1967 a twelve-string version and a three pickup version were introduced, the Melody Maker 12 and III respectively. A short length version of the Vibrola vibrato device was available as an option. From 1959 to 1964 the finish was a sunburst, from 1964 to 1965 it was cherry, from 1966 it was fire engine red or pelham blue, in 1967 red was replaced by sparkling burgundy and walnut became an option from 1968. Rare examples were made to order in other custom Gibson colors e.g. Inverness Green; this was the first Gibson Melody Maker that featured the devil-horn body style of the Gibson SG. This model featured a nitro laquer guitar finish in a variety of solid colors, it housed up to three single coil pickups similar to the P-90 pickup. All the guitars featured a stock Vibrola unit used to bend strings to alter the pitch of a note; the models were made with cheaper components for newer more inexperienced players. Gibson stopped production of these SG models in 1970 because of financial issues, they continued manufacturing the classic melody maker body style at various points throughout the years.

The Melody Maker was discontinued and replaced by the SG 100, 200 and 250. The Melody Maker double-cutaway model was revived in 1977 and discontinued again in 1983; some minor changes were introduced into the design including single coil pickups embossed with the Gibson logo, all metal tuning pegs and a latter-day Gibson stop tail piece and Tune-O-Matic bridge. In 1986, Gibson issued a Melody Maker with a single-cutaway body, it had one humbucking pickup, Grover tuners, a Tune-O-Matic bridge, a stop tailpiece. Two humbucking pickup models with two thumb switches were made but are hard to find; this rare model features Grover tuners, Kahler tremolo system and dual humbuckers. The body is standard single-cutaway Melody Maker; the finish is black with a pearloid pick guard. The Gibson All American II was built in the mid-1990s as part of the company's "All American" line which included The Hawk and The Paul II, it was inspired by the original Melody Maker, but differed from it in having chrome tuners, no scratchplate, controls rear-mounted in the traditional Gibson solid-body style, a bridge/vibrola unit.

The All American II featured two high output single coil pickups creating a tonality similar to a hotrodded telecaster than a typical Gibson instrument. The All American line was discontinued in 1998; the Melody Maker was returned to the Gibson line as a sub-model of the Les Paul model. It offered a mixture of traditional Melody Maker features and traditional Les Paul Junior features. Like both the original Melody Maker and the original Junior, the Les Paul Melody Maker featured dot inlays as fretboard markers and did not have a cap on its top. Unlike either the original Melody Maker or the original Junior, both of which used wraparaound bridge/tailpiece units, the Les Paul Melody Maker used a Tune-O-Matic bridge and separate stop tailpiece; the Les Paul Melody Maker differed from other Les Paul submodels in the width of the neck and the length of the heel. In 2007, the Melody Maker became a separate model, it now has a smaller single-coil pickup than the P-90, a wraparound bridge/tailpiece unit, a mahogany neck, a pickguard similar to the original Melody Maker.

The CEO of Gibson said in reference to the new Melody Maker that it could "almost be considered a reissue of a 1959 Gibson Melody Maker." The guitar is offered in satin finishes and is one of the most economical Gibson guitars in recent years. It was offered in single and dual pickup configurations; the dual pickup configuration was discontinued in 2008 and is now considered a collectors item on eBay In 2008 Gibson released the Joan Jett Signature Melody Maker. It differs from the standard model by having a single burstbucker 3 humbucker pickup, an ebony fretboard and a double-cutaway body in white with a black vinyl pickguard, it features a kill switch in place of a pickup selector. Jett has played it on all her hits, it retails for $839. There is now a "Blackheart" version of this guitar introduced in 2010. All specs are the same. In 2011 Gibson released the Flying V Melody Maker, Explorer Melody Maker, SG Melody Maker and the Les Paul Melody Maker. All feature a humbucker and 1 volume knob, at a MSRP of $829us.

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