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Journal articleYusuf NA, Green JL, Wall RJ, et al., 2015,
The Plasmodium Class XIV Myosin, MyoB, Has a Distinct Subcellular Location in Invasive and Motile Stages of the Malaria Parasite and an Unusual Light Chain
, Journal of Biological Chemistry, Vol: 290, Pages: 12147-12164, ISSN: 1083-351XMyosin B (MyoB) is one of the two short class XIV myosinsencoded in the Plasmodium genome. Class XIV myosins arecharacterized by a catalytic “head,” a modified “neck,” and theabsence of a “tail” region. Myosin A (MyoA), the other class XIVmyosin in Plasmodium, has been established as a component ofthe glideosome complex important in motility and cell invasion,but MyoB is not well characterized. We analyzed the propertiesof MyoB using three parasite species as follows: Plasmodiumfalciparum, Plasmodium berghei, and Plasmodium knowlesi.MyoB is expressed in all invasive stages (merozoites, ookinetes,and sporozoites) of the life cycle, and the protein is found in adiscrete apical location in these polarized cells. In P. falciparum,MyoB is synthesized very late in schizogony/merogony, and itslocation in merozoites is distinct from, and anterior to, that of arange of known proteins present in the rhoptries, rhoptry neckor micronemes. Unlike MyoA, MyoB is not associated withglideosome complex proteins, including the MyoA light chain,myosin A tail domain-interacting protein (MTIP). A uniqueMyoB light chain (MLC-B) was identified that contains a calmodulin-likedomain at the C terminus and an extended N-terminalregion. MLC-B localizes to the same extreme apical polein the cell as MyoB, and the two proteins form a complex. Wepropose that MLC-B is a MyoB-specific light chain, and for theshort class XIV myosins that lack a tail region, the atypical myosinlight chains may fulfill that role.
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Journal articleMasumoto N, Lanyon-Hogg T, Rodgers UR, et al., 2015,
Membrane bound O-acyltransferases and their inhibitors
, Biochemical Society Transactions, Vol: 43, Pages: 246-252, ISSN: 1470-8752Since the identification of the membrane-bound O-acyltransferase (MBOATs) protein family in the early2000s, three distinct members [porcupine (PORCN), hedgehog (Hh) acyltransferase (HHAT) and ghrelin Oacyltransferase(GOAT)] have been shown to acylate specific proteins or peptides. In this review, topologydetermination, development of assays to measure enzymatic activities and discovery of small moleculeinhibitors are compared and discussed for each of these enzymes.
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Journal articleCiepla P, Magee AI, Tate EW, 2015,
Cholesterylation: a tail of hedgehog
, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 43, Pages: 262-267, ISSN: 0300-5127- Author Web Link
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- Citations: 12
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Journal articleWright MH, Paape D, Storck EM, et al., 2015,
Global Analysis of Protein <i>N</i>-Myristoylation and Exploration of <i>N</i>-Myristoyltransferase as a Drug Target in the Neglected Human Pathogen <i>Leishmania donovani</i>
, CHEMISTRY & BIOLOGY, Vol: 22, Pages: 342-354, ISSN: 1074-5521- Author Web Link
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- Citations: 63
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Journal articleLanyon-Hogg T, Ritzefeld M, Masumoto N, et al., 2015,
Modulation of Amide Bond Rotamers in 5-Acyl-6,7-dihydrothieno[3,2-c]pyridines
, Journal of Organic Chemistry, Vol: 80, Pages: 4370-4377, ISSN: 1520-69042-Substituted N-acyl-piperidine is a widespread and important structuralmotif, found in approximately 500 currently available structures, and present in nearly30 pharmaceutically active compounds. Restricted rotation of the acyl substituent insuch molecules can give rise to two distinct chemical environments. Here wedemonstrate, using NMR studies and density functional theory modeling of the lowestenergy structures of 5-acyl-6,7-dihydrothieno[3,2-c]pyridine derivatives, that the amideE:Z equilibrium is affected by non-covalent interactions between the amide oxygen andadjacent aromatic protons. Structural predictions were used to design molecules that promote either the E- or Z-amideconformation, enabling preparation of compounds with a tailored conformational ratio, as proven by NMR studies. Analysis ofthe available X-ray data of a variety of published N-acyl-piperidine-containing compounds further indicates that these moleculesare also clustered in the two observed conformations. This finding emphasizes that directed conformational isomerism hassignificant implications for the design of both small molecules and larger amide-containing molecular architectures.
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Journal articleKonitsiotis AD, Jovanovic B, Ciepla P, et al., 2015,
Topological Analysis of Hedgehog Acyltransferase, a Multipalmitoylated Transmembrane Protein
, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 290, Pages: 3293-3307- Author Web Link
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- Citations: 46
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Journal articleTate EW, Kalesh KA, Lanyon-Hogg T, et al., 2015,
Global profiling of protein lipidation using chemical proteomic technologies
, CURRENT OPINION IN CHEMICAL BIOLOGY, Vol: 24, Pages: 48-57, ISSN: 1367-5931- Author Web Link
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- Citations: 80
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Journal articleDouse CH, Vrielink N, Zhang W, et al., 2015,
Targeting a Dynamic Protein-Protein Interaction: Fragment Screening against the Malaria Myosin A Motor Complex
, CHEMMEDCHEM, Vol: 10, Pages: 134-143, ISSN: 1860-7179- Author Web Link
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- Citations: 13
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Journal articleKalesh KA, Clulow JA, Tate EW, 2015,
Target profiling of zerumbone using a novel cell-permeable clickable probe and quantitative chemical proteomics
, CHEMICAL COMMUNICATIONS, Vol: 51, Pages: 5497-5500, ISSN: 1359-7345- Author Web Link
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- Citations: 27
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Journal articleFurse S, Mak L, Tate EW, et al., 2015,
Synthesis of unsaturated phosphatidylinositol 4-phosphates and the effects of substrate unsaturation on <i>Sop</i>B phosphatase activity
, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 13, Pages: 2001-2011, ISSN: 1477-0520- Author Web Link
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- Citations: 7
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