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Genomic preferred structures

The preferred modem procedure for investigating an enzyme mechanism is to identify a protein in a genome sequence, clone and express it, solve the crystal and/or solution structures, guess the mechanism, and then confirm it by site-directed mutagenesis and kinetics. The mechanism of lysozyme almost illustrates that procedure. Although the classical protein chemistry on lysozyme predated the molecular genetics, the kinetic studies were stimulated by the x-ray crystallography, and the previously unknown mechanism almost leapt from the... [Pg.240]

The enzyme is calcium-dependent, has a pH optimum of 8-10, and shows a striking preference for substrate presented in the form of Escherichia coli membranes. Using oligonucleotide probes based on amino-terminal sequence data, the corresponding human gene from a genomic DNA library, has been cloned and expressed in animal cells. The protein is secreted from cells in an active form. The deduced amino acid sequence of the human protein consists of 124 amino acids, contains structural features common to all known PLAjS, and has a half-cysteine pattern that is characteristic of the snake venom group II enzyme (60). [Pg.297]

Proteases have proven to be a favored target class for SBDD. Good crystal structures can often be obtained, substrate preferences are known, and the diseases involved (hypertension, HIV, HCV, etc.) are important ones with unmet needs. HIV protease was the second target to come along in AIDS after reverse transcriptase. Comparison of the HIV-1 viral genome with those of other retroviruses suggested that it too encoded for a protease. This protein, which proved to be necessary for the production of mature, infectious viral particles, was discovered to be an aspartyl protease smaller than those found in mammals, and it was proposed that it acted as a homodimer, which several X-ray structures of the enzyme published in 1989 confirmed. ... [Pg.303]


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See also in sourсe #XX -- [ Pg.316 ]




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Preferred structures

Structural genomics

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