C-10 deacetylase

Patel RN, Baneijee A, Nanduii W (2000) Enzymatic acetylation of 10-deacetylbaccatin III to baccatin IB by C-10 deacetylase liom Nocardioides luteus SC 13913. Enzyme Microb Technol 27 371-375... 

Figure 9 Hydrolysis of the C-10 acetate of taxanes by C-10 deacetylase from Nocardioides luteus SC 13912.

Paclitaxel and related compounds have also been found in various Taxus species in addition to the Pacific yew, occurring in roots, stems, wood, and needles as well as bark. Yew extracts contain a complex mixture of taxanes, with paclitaxel usually constituting less than 20% of the total taxanes. Isolation of paclitaxel from these mixtures is a difficult purification problem and contributed to the slow development of this compound as a drug. The most valuable material in this mixture for semisynthesis is 10-deacetylbaccatin-III. Microbial strains were isolated from soil samples containing C-13 deacylase and C-lO-deacetylase enzyme activities that are able to convert mixtures of taxanes to 10-deacetylbaccatin-III, thereby increasing the amount and ease of isolation of this precursor for semisynthesis (Scheme 17.14). Treatment of ethanol extracts, prepared either from whole plants of a variety of renewable yew cultivars or from material derived from the bark of... 

Fischer DD, Cai R, Bhatia U, Asselberg FA, Song C, Terry R, Trogani N, Widmer R, Atadja P, Cohen D (2002) Isolation and charaterization of a novel class II histone deacetylase, HDAC 10. J Biol Chem 277(8) 6656-6666... 

Verdel A, Curtet S, Brocard MP, Rousseaux S, Lemercier C, Yoshida M, Khochbin S (2000) Active maintenance of mHDA2/mHDAC6 histone-deacetylase in the cytoplasm. Curr Biol 10(12) ... 

Anderson KC (2004) Transcriptional signature of histone deacetylase inhibition in multiple myeloma Biological and clinical implications. Proc Natl Acad Sci USA 101 540-545 Moore SDP, Herrick SR, Ince TA, Klienman MS, Cin PD, Morton C, Quade BJ, 2000 Uterine Leiomyomata with t(10 17) disrupt the histone acetyltransferase MORF. Cancer Res 61 5570-5577 Morales V, Richard-Foy H (2000) Role of Histone N-Terminal Tails and Their Acetylation in Nucle-osome Dynamics. Mol Cell Biol 20 7230-7237... 

Wegener, D., Hildmann, C. and Schwienhorst, A. (2003) Recent progress in the development of assays suited for histone deacetylase inhibitor screening. Molecular Genetics and Metabolism,... 

Haggarty, S. J., Koeller, K. M., Wong, J. C., Butcher, R. A., and Schreiber, S. L. (2003) Multidimensional chemical genetic analysis of diversity-oriented synthesis-derived deacetylase inhibitors using cell-based assays. Chem. Biol. 10(5), 383-396. 

Coggins, B.E., Li, X., McClerren, A.L., Hindsgaul, O., Raetz, C.R.H., Zhou, P. Structure of the LpxC deacetylase with abound substrate-analog inhibitor. Nat Struct Biol 10 (2003) 645-651. 

Chitin is a stable compoimd, incompatible with oxidizing agents [59]. In the solid state imder alkaline condition (e.g., NaOH, KOH, heat at about 120 °C) or by enzymatic hydrolysis in the presence of a chitin deacetylase, it hydrolyses to form the deacetylated degradation product chitosan [6,7,10,11]. It was found that the presence of urea in basic media and at low temperature (—20 °C) had little effect on chitin structure and that urea is of benefit to the stability of chitin solution [38]. 

Class lib HDACs (6 and 10) are also characterized by homology to yeast HDA1, but possess two deacetylase-like domains. However, only in HDAC6 are both functional. The C-terminal catalytic domain of HDAC 10 is only partially present and does not retain activity [23, 24]. HDAC6 is ubiquitously expressed and cytoplasmic in location. It is promiscuous in its substrates which include chaperones, transmembrane proteins, a-tubulin, and cortactin [25-27]. HDAC10 has been identified as multiple splice variants. It is broadly expressed across cell types and has both a nuclear and cytosolic intracellular distribution. The C-terminal region contains putative retinoblastoma protein-binding domains [5]. 

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