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In muscle, assembly of ordered striated myofibrils requires the integration of hundreds of protein subunits in a sequential, regulated way by specific protein-protein interactions. The contractile filaments, composed of actin and myosin subunits, are crosslinked at the Z-disk and M-band, respectively, to give rise to a lateral assembly of molecular machines with nanometre precision. In the sarcomeric M-band, the giant ruler proteins titin and obscurin, its small homologue obscurin-like-1 ...
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Transposons are pieces of DNA that can jump from one place to another in the genome of a cell and they make up a surprisingly large proportion of many genomes. In creating genetic diversity they have had a strong influence on the evolution of genomes. If they transpose they can directly affect gene expression, by inserting into genes or gene regulatory elements. However, their activity is more often suppressed by silencing mechanisms such as DNA methylation or RNAi. The mutational activity ...
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Nicotinamidase catalyzes hydrolysis of nicotinamide to nicotinic acid and ammonia, in the NAD(+) salvage pathway. This enzyme activity has a fortuitous medical benefit since in Mycobacterium tuberculosis it converts the prodrug pyrazinamide nto the bacteriostatic pyrazinoic acid. Pyrazinoic acid is active against semidormant tubercle bacilli and together with rifampicin and isoniazid, forms the front line tuberculosis treatment. Studies of the enzyme have revealed aspects of structure ...
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The regulation of the alternative splicing of messenger RNA allows mammals and other eukaryotic organisms to greatly enrich the diversity of the proteins coded by their genomes. Most eukaryotic genes are fragmented into introns that need to be joined up before the encoded protein is synthesised. But by combining the introns in different ways, the cell can make different proteins from the same genetic material.
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A protein complex called MRE11-RAD50-NBS1 (MRN) coordinates the detection and repair of one of the most hazardous forms of DNA damage, the double strand break (DSB), in which both strands of a DNA helix are cut. The nuclease and scaffolding components of MRN, MRE11 and RAD50 respectively, have been widely studied at the molecular level, however the molecular basis of NBS1 function remains undefined. Using beamline I04 at Diamond we have been able to solve a 2.3 Å crystal structure of the ...
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Polycomb group proteins have an essential role in maintaining repressive epigenetic states and silencing unwanted gene expression during development. Disregulation of polycomb proteins have also been implicated in many types of cancer. Polycomb Repressive Complex 2 (PRC2) is the key enzyme complex that marks repressive chromatin domains by methylating lysine 27 of histone H3. PRC2 is composed of four ubunits, EZH2, which contains the catalytic SET domain, EED, Suz12 and RbAp48. Using ...
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The three-dimensional structure of [NiFeSe] hydrogenase from D. vulgaris Hildenborough in its oxidised, “as isolated” state has been determined from a 3-wavelength MAD experiment at the Fe K-edge on Diamond Beamline I04. Crystals were obtained in space group P21 with cell parameters a = 60.6, b = 91.2, c = 66.7 Å, b = 101.7º and one hydrogenase molecule in the asymmetric unit. This work has recently been published [1]. Previously, only the structure of [NiFeSe] hydrogenase from Dm. baculatum ...
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The structure of a protein complex between a bacterial and a human protein solved using data collected at Diamond Light Source (UK) and the ESRF (FRANCE) has revealed the way in which bacteria that cause bacterial meningitis mimic human cells to evade the body’s innate immune system. The study, published in Nature, could lead to the development of new vaccines that give better protection against meningitis B, the strain which accounts for the vast majority of cases of the disease in the UK.
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Violerythrin, a blue colored carotenoid, has been investigated by X-ray crystallography and by steady-state and ultrafast time-resolved absorption spectroscopy.
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Seasonal epidemics and worldwide pandemics caused by influenza A viruses are of continuous public health concern. During infection, the viral nonstructural (NS1) protein stimulates phosphoinositide 3-kinase (PI3K) signaling, an essential cell survival pathway commonly mutated in human cancers. A structure of the NS1 effector domain in complex with the p85β inter-SH2 (coiled-coil) domain suggests that NS1 uses the coiled-coil as a structural tether to sterically prevent normal inhibitory ...
Macromolecular
Soft Condensed 
Imaging and
Biological
Magnetic
Structures and
Crystallography 
Spectroscopy 