tion dependence observed for Vi trapping with ADP/ATP; (f) the kinetics 
observed for Vi predict occlusion on the nucleotide (equivalent to trapping without having Vi). This arises mostly from formation of your Adjudin structure species E ATP (and FATP ) as a consequence of slower conversion of E ATP P, as well as enhanced formation by dissociation of which constructed as much as a larger steady-state concentration simply because of drastically decreased hydrolysis. We decreased k0 and k{0 by 1000-fold for the Pgp mutants and assumed that after passage 9723954 through a gel filtration column (,30 s) almost all of the twonucleotide species become one-nucleotide species (since k{1 100s{1 , ,2000k{0 ). Figure S2B shows the fraction of Pgp with retained nucleotide (i.e. occluded species) at various ATP Figure 12. Cartoons depicting the Alternating Cycle. (A) Random binding model adapted from Urbatsch et al. [32]. (B) Sequential binding model proposed in this work (see Figure 2). White triangles represent ATP, black triangles represent ATP committed for hydrolysis; ADPPi is shown in red, ADP in white. The subscripts of the intermediates (A to F) correspond to the N and C terminal halves of the protein. Closure of the NBD dimer interface is reflected in the fusion of both halves of the protein square. Flow through each half-cycle is represented by the blue and red arrows. trapping with ADP; (g) the kinetics observed for Vi release from the trapped-species; and (h) detection of species with only one trapped nucleotide. Development of the Extended Alternating Cycle allowed us to include additional kinetic steps to account for most of the deficiencies (c)-(h) of the original model (however, observations (a) and (b) still remain unexplained). Figure 9 summarizes the ATP dependence of several biochemical variables in the PE Alternating Cycle of Pgp, according to the parameters given in Tables 2 and 3. This proposed model introduces both priming and trapping reactions into the kinetic scheme, and is able to account for the observed high affinity of Pgp for ATP without any reference to the occluded state, thus avoiding assigning special properties to any intermediate in the cycle. A new interpretation of the occlusion phenomenon also emerges from the model. Future work will be needed to model a comprehensive reaction scheme to explain the complete data-set of biochemical observations.Dengue virus (DENV), a flavivirus within the Flaviviridae family, is the most 11543771” common mosquito-borne viral infectious agent worldwide. According to new estimates, 390 million DENV infections occur annually, of which about 100 million are symptomatic [1]. There are four different serotypes of DENV. Each of them can cause disease ranging from rather mild dengue fever to more severe dengue hemorrhagic fever and dengue shock syndrome [2,3]. Pre-existing heterotypic antibodies represent a major risk factor for the development of severe disease via antibody-dependent enhancement of disease (ADE) [4]. In ADE, pre-existing cross-reactive antibodies are hypothesized to bind to the newly infecting virus and facilitate efficient replication in Fcy-receptor-expressing cells, thereby increasing the infected cell mass and viral load. A high viral load is often a prelude for severe disease development [7]. DENV-infected cells secrete a heterogeneous population of virions that vary in maturation state [82]. Junjhon and colleagues showed that more than 90% of the particles secreted from C6/36 cells contain at least some prM molecules [8]. Structural work dem