Browsing by resource type "preprint"
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- An alternative proposal for the reaction mechanism of light-dependent protochlorophyllide oxidoreductasePublication . Silva, Pedro J.; Cheng, QiLight-dependent protochlorophyllide oxidoreductase is one of the few known enzymes that require a quantum of light to start their catalytic cycle. Upon excitation, it uses NADPH to reduce the C17–C18 in its substrate (protochlorophyllide) through a complex mechanism that has heretofore eluded precise determination. Isotopic labeling experiments have shown that the hydride-transfer step is very fast, with a small barrier close to 9 kcal mol–1, and is followed by a proton-transfer step, which has been postulated to be the protonation of the product by the strictly conserved Tyr189 residue. Since the structure of the enzyme–substrate complex has not yet been experimentally determined, we first used modeling techniques to discover the actual substrate binding mode. Two possible binding modes were found, both yielding stable binding (as ascertained through molecular dynamics simulations) but only one of which placed the critical C17═C18 bond consistently close to the NADPH pro-S hydrogen and to Tyr189. This binding pose was then used as a starting point for the testing of previous mechanistic proposals using time-dependent density functional theory. The quantum-chemical computations clearly showed that such mechanisms have prohibitively high activation energies. Instead, these computations showed the feasibility of an alternative mechanism initiated by excited-state electron transfer from the key Tyr189 to the substrate. This mechanism appears to agree with the extant experimental data and reinterprets the final protonation step as a proton transfer to the active site itself rather than to the product, aiming at regenerating it for another round of catalysis.
- Economic and Monetary Union: insights into the theoretical conundrum of European IntegrationPublication . Vila Maior, Paulo; noAs part of an ongoing research, this paper focus on European monetary integration depicting to what extent existing theories and theoretical approaches fit with the ontology and subsequent developments of Economic and Monetary Union (EMU). A special emphasis goes to the Stability and Growth Pact (SGP) as a crucial ingredient of European monetary integration, particularly for the political turmoil it produced in recent years. On a previous conference (UACES Annual Conference 2007: Exchanging Ideas on Europe: Common Values and External Policies, Portsmouth, UK, 3-5 September 2007), EMU and the SGP were assessed through the lens of neofunctionalism, liberal intergovernmentalism, supranational governance, new institutionalism and the fusion thesis. This paper turns to the federal theory and the rational choice theory. Some argue that the power of ideas (the monetarist school) and national governments’ adjustment to a new international setting provide the broad explanation of the move towards EMU. Others claim that the project of European monetary integration was independent from such exogenous inputs, understanding the step towards EMU as part of the dynamism encapsulated by European integration. I test these contrasting perceptions against the explanatory power of federal theory and rational choice. The analysis of the SGP (in both the original version and after the November 2005 reform) follows the same methodology. The rationale behind the paper is twofold. On the one hand, whether EMU and the SGP fit into one of the theories under examination, and whether the corresponding mapping is telling of theoretical prevalence or dissemination. On the other hand, whether the SGP (and subsequent reform) converges or diverges with EMU’s theoretical matrix.
- Prevalence of Neisseria gonorrhoeae and Trichomonas vaginalis in portuguese women of childbearing agePublication . Silva, Jani; Cerqueira, Fátima; Teixeira, Ana Luísa; Campainha, Rui; Amorim, José; Medeiros, R.
- Response to “molecular-level understanding of biological energy coupling and transduction: response to “chemiosmotic misunderstandings”Publication . Silva, Pedro J.The most recent contribution by Sunil Nath in these pages is, mostly, a repetition of his previous claims regarding failures of the chemiosmotic hypotheses, supplemented with some fresh misunderstandings of the points I had sought to clarify in my previous critique. Considerable portions rehash 50-60 years-old controversies, with no apparent understanding that the current chemiosmotic hypothesis, while birthed by Mitchell, differs from Mitchell's details in many respects. As such, Nath has devoted much time dealing with a few errors (or wrong hypotheses) by Mitchell (in a few places I would almost venture to say "typographical mistakes in typesetting") and presents the ensuing conclusions as "refutations" of the chemiosmotic paradigm, completely neglecting that such details (such as the precise H+/ATP or H+:O ratios) are completely irrelevant to the reality (or not) of an electron-transport chain that uses the free energy liberated by electron-transfer to remove H+ from a compartment, to which it returns through and ATP synthase which uses the energy in that spontaneous return to drive ATP synthesis. The thermodynamical mistakes and misunderstandings of the relevant literature present in Nath's new contribution are so numerous, though, that I feel forced to call the attention of the readers of "Biophysical Chemistry" to them.