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21.
Chiung-Kuang J. Chen Robert E. Berry Tatjana Kh. Shokhireva Marat B. Murataliev Hongjung Zhang F. Ann Walker 《Journal of biological inorganic chemistry》2010,15(2):159-174
CYP102A1 is a highly active, water-soluble, bacterial monooxygenase enzyme that contains both substrate-binding heme and diflavin
reductase subunits, both in a single polypeptide. Recently we developed a procedure which uses the known structure of the
substrate-bound heme domain of CYP102A1 and its sequence homology with a cytochrome P450 of unknown structure, both of which
react with a common substrate but produce different products, to create recombinant enzymes which have substrate selectivity
different from that of CYP102A1, and produce the product of the enzyme of unknown structure. Insect CYP4C7, a terpene hydroxylase
from the cockroach, was chosen as the cytochrome P450 of unknown structure, and farnesol was chosen as the substrate. CYP102A1
oxidizes farnesol to three products (2,3-epoxyfarnesol, 10,11-epoxyfarnesol, and 9-hydroxyfarnesol), whereas CYP4C7 produces
12-hydroxyfarnesol as the major product. In earlier work it was found that the chimera C(78-82,F87L) showed a change in substrate
selectivity from fatty acids to farnesol, and was approximately sixfold more active than wild-type CYP102A1 (Chen et al. in
J Biol Inorg Chem 13:813–824, 2008), but neither it nor any other earlier chimera produced 12-hydroxyfarnesol. In this work we added amino acid residues 327–332,
to create six new full-length, functional chimeric proteins. Four of these, the most active of which was C(78-82,F87L,328-330),
produce 12-hydroxyfarnesol as the major product, with approximately twofold increase in turnover number as compared with wild-type
CYP102A1 toward farnesol. Methylfarnesoate was metabolized to 12-hydroxymethylfarnesoate (70%) and 10,11-epoxymethylfarnesoate
(juvenile hormone III) (30%). The latter is metabolized to 65% 12-hydroxy-10,11-epoxymethylfarnesoate and 35% 15-hydroxy-10,11-epoxymethylfarnesoate.
Substitution of residues 328–330, APA, by VPL was crucial to accomplishing this change in product. 相似文献
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BUALUANG FAIYUE MOHAMMED J. AL‐AZZAWI TIMOTHY J. FLOWERS 《Plant, cell & environment》2010,33(5):702-716
Although an apoplastic pathway (the so‐called bypass flow) is implicated in the uptake of Na+ by rice growing in saline conditions, the point of entry of this flow into roots remains to be elucidated. We investigated the role of lateral roots in bypass flow using the tracer trisodium‐8‐hydroxy‐1,3,6‐pyrenetrisulphonic acid (PTS) and the rice cv. IR36. PTS was identified in the vascular tissue of lateral roots using both epifluorescence microscopy and confocal laser scanning microscopy. Cryo‐scanning electron microscopy and epifluorescence microscopy of sections stained with berberine‐aniline blue revealed that the exodermis is absent in the lateral roots. We conclude that PTS can move freely through the cortical layers of lateral roots, enter the stele and be transported to the shoot via the transpiration stream. 相似文献
24.
Wu LY Anderson MO Toriyabe Y Maung J Campbell TY Tajon C Kazak M Moser J Berkman CE 《Bioorganic & medicinal chemistry》2007,15(23):7434-7443
To identify the pharmacophore of a phosphoramidate peptidomimetic inhibitor of prostate-specific membrane antigen (PSMA), a small analog library was designed and screened for inhibitory potency against PSMA. The design of the lead inhibitor was based upon N-acyl derivatives of endogenous substrate folyl-gamma-Glu and incorporates a phosphoramidate group to interact with the PSMA catalytic zinc atoms. The scope of the analog library was designed to test the importance of various functional groups to the inhibitory potency of the lead phosphoramidate. The IC(50) for the lead phosphoramidate inhibitor was 35 nM while the IC(50) values for the analog library presented a range from 0.86 nM to 4.1 microM. Computational docking, utilizing a recently solved X-ray crystal structure of the recombinant protein, along with enzyme inhibition data, was used to propose a pharmacophore model for the PSMA active site. 相似文献
25.
Identification of the amino acids essential for LytSR‐mediated signal transduction in Staphylococcus aureus and their roles in biofilm‐specific gene expression 下载免费PDF全文
26.
Gopinath Kulasekaran Nadya Nossova Andrea L. Marat Ingrid Lund Christopher Cremer Maria S. Ioannou Peter S. McPherson 《The Journal of biological chemistry》2015,290(29):17999-18008
Connecdenn 1/2 are DENN (differentially expressed in normal and neoplastic cells) domain-bearing proteins that function as GEFs (guanine nucleotide exchange factors) for the small GTPase Rab35. Disruption of connecdenn/Rab35 function leads to defects in the recycling of multiple cargo proteins from endosomes with altered cell function, yet the regulation of connecdenn GEF activity is unexplored. We now demonstrate that connecdenn 1/2 are autoinhibited such that the purified, full-length proteins have significantly less Rab35 binding and GEF activity than the isolated DENN domain. Both proteins are phosphorylated with prominent phosphorylation sites between residues 500 and 600 of connecdenn 1. A large scale proteomics screen revealed that connecdenn 1 is phosphorylated at residues Ser-536 and Ser-538 in an Akt-dependent manner in response to insulin stimulation of adipocytes. Interestingly, we find that an Akt inhibitor reduces connecdenn 1 interaction with Rab35 after insulin treatment of adipocytes. Remarkably, a peptide flanking Ser-536/Ser-538 binds the DENN domain of connecdenn 1, whereas a phosphomimetic peptide does not. Moreover, connecdenn 1 interacts with 14-3-3 proteins, and this interaction is also disrupted by Akt inhibition and by mutation of Ser-536/Ser-538. We propose that Akt phosphorylation of connecdenn 1 downstream of insulin activation regulates connecdenn 1 function through an intramolecular interaction. 相似文献
27.
Wang T Ioannidis S Almeida L Block MH Davies AM Lamb ML Scott DA Su M Zhang HJ Alimzhanov M Bebernitz G Bell K Zinda M 《Bioorganic & medicinal chemistry letters》2011,21(10):2958-2961
Synthesis and biological evaluation of a series of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors was reported. Biochemical screening, followed by profile optimization, resulted in JAK2 inhibitors exhibiting good kinase selectivity, pharmacokinetic properties, physical properties and pharmacodynamic effects. 相似文献
28.
Andrey Bogoyavlenskiy Vladimir Berezin Alexey Prilipov Ilya Korotetskiy Irina Zaitseva Aydyn Kydyrmanov Kobey Karamedin Nailya Ishmukhametova Saule Asanova Marat Sayatov Kainar Zhumatov 《Virologica Sinica》2011,(6)
Although the important role of the non-structural (NS1 and NEP) gene of influenza A in virulence of the virus is well established, our knowledge about the extent of variation in the NS gene pool of influenza A viruses in their natural reservoirs in Kazakhstan is incomplete. 17 influenza A viruses of different subtypes were studied in this paper. Seven types of haemagglutinin and five different neuraminidase subtypes in eight combinations were found among the isolated viruses. A comparison of nucleotide sequ... 相似文献
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