Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A simple ligand-protein structural optimization and binding evaluation procedure has been routinely used in high-speed ligand-protein docking studies. In this work, we examine whether such an optimization/scoring procedure is useful in indicating possible drug-resistant mutations in proteins. Crystal structures of three wild-type enzymes (HIV-1 protease, HIV-1 reverse transcriptase, and Mycobacterium tuberculosis H37Rv enoyl-ACP reductase) complexed to a variety of inhibitors are studied. Mutations are introduced into these structures by using the molecular modeling software, SYBYL. Structural optimization and scoring of a mutant complex is conducted by a procedure similar to that used in a recent docking study (Wang et al., 1999). The computed results are compared with observed drug resistance data and the profile of nonresistant mutations. Most mutations studied show an energy change in the same direction as those indicated by observed resistance data. 50% of the polar to polar or nonpolar to nonpolar mutations are found to correlate qualitatively with observed drug resistance data. Van der Waals interactions account for most of these changes, which is in agreement with conclusions from structural studies. Substantially larger deviations are found between computed results and observed data for most polar to nonpolar or nonpolar to polar mutations, which result from deficiency in modelling and scoring ligand-protein interactions in our procedure. Our results suggest that an optimization/docking scoring procedure is useful for qualitatively probing polar to polar or nonpolar to nonpolar resistant mutations in addition to its application in screening active compounds. More accurate description of ligand-protein interactions and the use of methods such as free energy perturbation and Poisson-Boltzmann may be needed to further improve the quality of prediction.
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PMID:Can an optimization/scoring procedure in ligand-protein docking be employed to probe drug-resistant mutations in proteins? 1155 85

In plants, fatty acid and complex lipid synthesis requires the correct spatial and temporal activity of many gene products. Quantitative northern analysis showed that mRNA for the biotin carboxylase subunit of heteromeric acetyl-coenzyme A carboxylase, fatty acid synthase components (3-oxoacyl-acyl carrier protein [ACP] reductase, enoyl-ACP reductase, and acyl-ACP thioesterase), and stearoyl-ACP desaturase accumulate in a coordinate manner during Brassica napus embryogenesis. The mRNAs were present in a constant molar stoichiometric ratio. Transcript abundance of mRNAs for the catalytic proteins was found to be similar, whereas the number of ACP transcripts was approximately 7-fold higher. The peak of mRNA accumulation of all products was between 20 and 29 d after flowering; by 42 d after flowering, the steady-state levels of all transcripts fell to about 5% of their peak levels, which suggests that the mRNAs have similar stability and kinetics of synthesis. Biotin carboxylase was found to accumulate to a maximum of 59 fmol mg(-1) total RNA in embryos, which is in general agreement with the value of 170 fmol mg(-1) determined for Arabidopsis siliques (J.S. Ke, T.N. Wen, B.J. Nikolau, E.S. Wurtele [2000] Plant Physiol 122: 1057-1071). Embryos accumulated between 3- and 15-fold more transcripts per unit total RNA than young leaf tissue; the lower quantity of leaf 3-oxoacyl-ACP reductase mRNA was confirmed by reverse transcriptase-polymerase chain reaction. This is in conflict with analysis of B. napus transcripts using an Arabidopsis microarray (T. Girke, J. Todd, S. Ruuska, J. White, C. Benning, J. Ohlrogge [2000] Plant Physiol 124: 1570-1581) where similar leaf to seed levels of fatty acid synthase component mRNAs were reported.
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PMID:Fatty acid and lipid biosynthetic genes are expressed at constant molar ratios but different absolute levels during embryogenesis. 1201 61