In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Input: Consider Input: Many viruses have been implicated in utilizing or modulating the Ubiquitin Proteasome System (UPS) to enhance viral multiplication and/or to sustain a persistent infection. The mosquito-borne Venezuelan equine encephalitis virus (VEEV) belongs to the Togaviridae family and is an important biodefense pathogen and select agent. There are currently no approved vaccines or therapies for VEEV infections; therefore, it is imperative to identify novel targets for therapeutic development. We hypothesized that a functional UPS is required for efficient VEEV multiplication. We have shown that at non-toxic concentrations Bortezomib, a FDAapproved inhibitor of the proteasome, proved to be a potent inhibitor of VEEV multiplication in the human astrocytoma cell line U87MG. Bortezomib inhibited the virulent Trinidad donkey (TrD) strain and the attenuated TC-83 strain of VEEV. Additional studies with virulent strains of Eastern equine encephalitis virus (EEEV) and Western equine encephalitis virus (WEEV) demonstrated that Bortezomib is a broad spectrum inhibitor of the New World alphaviruses. Time-of-addition assays showed that Bortezomib was an effective inhibitor of viral multiplication even when the drug was introduced many hours post exposure to the virus. Mass spectrometry analyses indicated that the VEEV capsid protein is ubiquitinated in infected cells, which was validated by confocal microscopy and immunoprecipitation assays. Subsequent studies revealed that capsid is ubiquitinated on K48 during early stages of infection which was affected by Bortezomib treatment. This study will aid future investigations in identifying host proteins as potential broad spectrum therapeutic targets for treating alphavirus infections.

Output: The Ubiquitin Proteasome System Plays a Role in Venezuelan Equine Encephalitis Virus Infection

Input: Consider Input: ('filoviruses') that cause severe hemorrhagic fever with human case fatality rates of up to 90%. Filovirus infection requires fusion of the host cell and virus membranes, a process that is mediated by the envelope glycoprotein (GP). GP contains two subunits, the surface subunit (GP1), which is responsible for cell attachment, and the transmembrane subunit (GP2), which catalyzes membrane fusion. The GP2 ectodomain contains two heptad repeat regions, N-terminal and C-terminal (NHR and CHR, respectively) that adopt a six-helix bundle during the fusion process. The refolding of this six-helix bundle provides the thermodynamic driving force to overcome barriers associated with membrane fusion. Here we report the crystal structure of the MARV GP2 core domain in its post-fusion (six-helix bundle) conformation at 1.9 A resolution. The MARV GP2 core domain backbone conformation is virtually identical to that of EBOV GP2 (reported previously), and consists of a central NHR core trimeric coiled-coil packed against peripheral CHR -helices and an intervening loop/helix-turn-helix segment. We previously reported that the stability of the MARV GP2 post-fusion structure is highly pH-dependent, with increasing stability at lower pH [Harrison, J.S.; Koellhoffer, J. K.; Chandran, K.; and Lai, J. R. Biochemistry, 2012Biochemistry, , 51, 2515Biochemistry, -2525. We hypothesized that this pH-dependent stability provides a mechanism for conformational control such that the post-fusion six helix bundle is promoted in the environments of appropriately matured endosomes. In this report, a structural rationale for this pH-dependent stability is described, and involves a high-density array of core and surface acidic side chains at the midsection of the structure, termed the 'anion stripe.' In addition, many surface-exposed salt bridges likely contribute to stabilizing the post-fusion structure at low pH. These results provide structural insights into the mechanism of MARV GP2-mediated membrane fusion.

Output: Crystal Structure of the Marburg Virus GP2 Core Domain in its Post-Fusion Conformation

Input: Consider Input: Glycosyltransferases (GTs) are bidirectional biocatalysts catalyzing the glycosylation of diverse molecules. However, the extensive applications of GTs in glycosides formation are limited due to their requirements of expensive nucleotide diphosphate (NDP)-sugars or NDP as the substrates. Here, in an effort to characterize flexible GTs for glycodiversification of natural products, we isolated a cDNA, designated as OcUGT1 from Ornithogalum caudatum, which encoded a flavonoid GT that was able to catalyze the trans-glycosylation reactions, allowing the formation of glycosides without the additions of NDP-sugars or NDP. In addition, OcUGT1 was observed to exhibit additional five types of functions, including classical sugar transfer reaction and three reversible reactions namely NDP-sugar synthesis, sugars exchange and aglycons exchange reactions, as well as enzymatic hydrolysis reaction, suggesting OcUGT1 displays both glycosyltransferase and glycosidase activities. Expression profiles revealed that the expression of OcUGT1 was development-dependent and affected by environmental factors. The unusual multifunctionality of OcUGT1 broadens the applicability of OcUGT1, thereby generating diverse carbohydrate-containing structures. Glycosylation is one of the most important modification reactions, in which sugar moieties are transferred to small molecular acceptors thereby leading to the formation of diverse glycosides with therapeutical potentials 1 . The enzyme-based glycosylations are mainly performed by two types of carbohydrate-active enzymes (CAZymes), glycosyltransferases (GTs, EC 2.4.x.y) and glycosidases (glycoside hydrolases; EC 3.2.x.y) 2 . Glycosidases are naturally hydrolytic enzymes that normally cleave glycosidic bonds 3 . However, glycosidase-assisted glycosylations are able to be achieved by trans-glycosylation reactions under certain controlled conditions 4 . The majority of glycosylation reactions in nature are performed in GT-catalyzed fashion, in which the carbohydrate moieties from activated NDP-sugars are transferred to acceptor molecules 5 . Also, GT-catalyzed glycosylations were accomplished by running the GT reactions in reverse 6 . New glycosides can be generated by reversible sugar or aglycon exchange reactions catalyzed by GTs with the addition of excess of NDP 6,7 . It is therefore obvious that GTs are generally perceived as bidirectional biocatalysts used in glycosylation of small molecules 1, 8, 9 . Yet, despite the validated potential of GTs in glycosides production, the extensive applications of GTs in industry remained limited due to the requirement of expensive NDP-sugars or NDP in GT-catalyzed forward or reversible reactions. Here, we report that a flavonoid GT, designated as OcUGT1, catalyzes the trans-glycosylation reactions, allowing the formation of glycosides without the additions of NDP-sugars or NDP. Specifically, in a screen of novel biocatalysts for flavonoid glycosylations from medicinal plant Ornithogalum caudatum, we found a multifunctional flavonoid GT OcUGT1 exhibiting at least six types of functions, including classical sugar transfer reaction and three reversible reactions namely NDP-sugar synthesis, sugars exchange and aglycons exchange reactions, as well as glycosidase specific hydrolysis and trans-glycosylation reactions. These evidences indicated that OcUGT1 shows
Output: Isolation and characterization of a multifunctional flavonoid glycosyltransferase from Ornithogalum caudatum with glycosidase activity OPEN