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Porphyrin Binding and Distortion and Substrate Specificity in the Ferrochelatase Reaction: The Role of Active Site Residues.

The specific insertion of a divalent metal ion into tetrapyrrole macrocycles is catalyzed by a group of enzymes called chelatases. Distortion of the tetrapyrrole has been proposed to be an important component of the mechanism of metallation. We present the structures of two different inhibitor complexes: (1) N-methylmesoporphyrin (N-MeMP) with the His183Ala variant of Bacillus subtilis ferrochelat

Possible sites of action of the new calcitonin gene-related peptide receptor antagonists.

Migraine is considered a neurovascular disease affecting more than 10% of the general population. Currently available drugs for the acute treatment of migraine are vasoconstrictors, which have limitations in their therapeutic use. The calcitonin gene-related peptide (CGRP) has a key role in migraine, where levels of CGRP are increased during acute migraine attacks. CGRP is expressed throughout the

Short and simple sequences favored the emergence of N-helix phospho-ligand binding sites in the first enzymes

The ubiquity of phospho-ligands suggests that phosphate binding emerged at the earliest stage of protein evolution. To evaluate this hypothesis and unravel its details, we identified all phosphate-binding protein lineages in the Evolutionary Classification of Protein Domains database. We found at least 250 independent evolutionary lineages that bind small molecule cofactors and metabolites with ph

Evaluating a new hydraulic implementation in LPJ-GUESS for three sites in north Europe

Drought is projected to increase in frequency and intensity and impacts trees with increased water stress and increased mortality rate. Water stresses can cause hydraulic failure-related mortality or carbon starvation due to tree species having different strategies to deal with water stresses. LPJ-GUESS-HYD (Hydraulic implementation of a new plant hydraulics scheme in LPJ-GUESS) was developed to i

Carbon stocks and fluxes in the high latitudes : Using site-level data to evaluate Earth system models

It is important that climate models can accurately simulate the terrestrial carbon cycle in the Arctic due to the large and potentially labile carbon stocks found in permafrost-affected environments, which can lead to a positive climate feedback, along with the possibility of future carbon sinks from northward expansion of vegetation under climate warming. Here we evaluate the simulation of tundra

Analysis of binding sites on complement factor I using artificial N-linked glycosylation.

Factor I (FI) is a serine protease that inhibits all complement pathways by degrading activated complement components C3b and C4b. FI functions only in the presence of several cofactors such as factor H, C4b-binding protein, complement receptor 1 and membrane cofactor protein. FI is composed of two chains linked by a disulphide bridge; the light chain comprises only the serine protease (SP) domain

Comparing Scots pine tree-ring proxies and detrending methods among sites in Jamtland, west-central Scandinavia

Scots pine tree-ring width (TRW) data from Jamtland in the Central Scandinavian Mountains has been used to reconstruct summer temperatures back to 1630 BC. However, it was recently shown that this reconstruction was of limited spatial importance. In this paper, we aim to explain this limitation in the TRW data as a temperature proxy, as well as assess the temperature information from new maximum l