Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “MUTATIONS”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase

The structure of a phenylalanine aminomutase (TcPAM) from Taxus canadensis has been determined at 2.4 {angstrom} resolution. The active site of the TcPAM contains the signature 4-methylidene-1H-imidazol-5(4H)-one prosthesis, observed in all catalysts of the class I lyase-like family. This catalyst isomerizes (S)-{alpha}-phenylalanine to the (R)-{beta}-isomer by exchange of the NH{sub 2}/H pair. The stereochemistry of the TcPAM reaction product is opposite of the (S)-{beta}-tyrosine made by the mechanistically related tyrosine aminomutase (SgTAM) from Streptomyces globisporus. Since TcPAM and SgTAM share similar tertiary- and quaternary-structures and have several highly conserved aliphatic residues positioned analogously in their active sites for substrate recognition, the divergent product stereochemistries of these catalysts likely cannot be explained by differences in active site architecture. The active site of the TcPAM structure also is in complex with (E)-cinnamate; the latter functions as both a substrate and an intermediate. To account for the distinct (3R)-{beta}-amino acid stereochemistry catalyzed by TcPAM, the cinnamate skeleton must rotate the C{sub 1}-C{sub {alpha}} and C{sub ipso}-C{sub {beta}} bonds 180{sup o} in the active site prior to exchange and rebinding of the NH{sub 2}/H pair to the cinnamate, an event that is not required for the corresponding acrylate intermediate in the SgTAM reaction. Moreover, the aromatic ring of the intermediate makes only one direct hydrophobic interaction with Leu-104. A L104A mutant of TcPAM demonstrated an 1.5-fold increase in k{sub cat} and a decrease in K{sub M} values for sterically demanding 3'-methyl-{alpha}-phenylalanine and styryl-{alpha}-alanine substrates, compared to the kinetic parameters for TcPAM. These parameters did not change significantly for the mutant with 4'-methyl-{alpha}-phenylalanine compared to those for TcPAM.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2015

Analysis of mutational signatures in exomes from B-cell lymphoma cell lines suggest APOBEC3 family members to be involved in the pathogenesis of primary effusion lymphoma

Here, primary effusion lymphoma (PEL) is a rare large B-cell neoplasm particularly affecting immunodeficient hosts with an increased incidence in young or middle-aged males infected with the HIV. 1 The clinical outcome of patients with PEL is unfavorable with a median survival of <6 months. 1 PEL has been closely associated with human herpes virus 8 (HHV8, previously called Kaposi sarcoma herpesvirus) infection. 1 In some cases a coinfection of HHV8 with the Epstein–Barr Virus (EBV) has been described. 1 HHV8 encodes various genes homologous to cellular genes that have proliferative and anti-apoptotic functions. 2 Although HHV8 is supposed to be a major driver of PEL, it alone is not sufficient for a full-blown lymphomagenesis. 2 PEL usually shows complex karyotypes with many chromosomal aberrations. 3 This chromosomal complexity might be driven by the viral infection and lead to genetic alterations cooperating with HHV8 in PEL lymphomagenesis. 4

59 BASIC BIOLOGICAL SCIENCES↗