Cryo-EM structures of human fucosidase FucA1 reveal insight into substrate recognition and catalysis

Enzymatic hydrolysis of α-L-fucose from fucosylated glycoconjugates is consequential in bacterial infections and the neurodegenerative lysosomal storage disorder fucosidosis. Understanding human α-L-fucosidase catalysis, in an effort toward drug design, has been hindered by the absence of three-dimensional structural data for any animal fucosidase. Here, we have used cryoelectron microscopy (cryo-EM) to determine the structure of human lysosomal α-L-fucosidase (FucA1) in both an unliganded state and in complex with the inhibitor deoxyfuconojirimycin. These structures, determined at 2.49 Å resolution, reveal the homotetrameric structure of FucA1, the architecture of the catalytic center, and the location of both natural population variations and disease-causing mutations. Furthermore, this work has conclusively identified the hitherto contentious identity of the catalytic acid/base as aspartate-276, representing a shift from both the canonical glutamate acid/base residue and a previously proposed glutamate residue. These findings have furthered our understanding of how FucA1 functions in both health and disease.Bio-organic Synthesi

A simplified model for buckling mechanism in lattice structures

This paper presents a simplified model of buckling mechanism which occurs in slender steel column elements under compressive axial loading. This model has been used to predict buckling capacities of certain structures, and comparisons have been made with test results. The method presented is not as accurate as the current finite element methods which use complete large displacement elasto-plastic analysis. However, it provides a reasonable upper bound load very economically, and with reasonable accuracy. It will be argued that it is pointless striving for a 1% accuracy when material parameters and load target values themselves can only be accurate to, say, 10%. The study has used software developed by Meek [3DBUCKLE-eigenvalue analysis program for buckling of steel columns, University of Queensland (1973)], which uses eigenvalue analysis by iteration to determine the Euler (theoretical) value of the buckling load of a column structure. This program was adapted to include the possibility that, during buckling, a reduced modulus section develops at the central portion of the critical column length. The reduction in the second moment of area of the section over a given length ensures that the revised estimate of the failure load is less than that predicted by the Euler formula for the undamaged column. The program was used to predict the failure loads of structures previously tested in other research programs, and the results show reasonable agreement with experiment. The paper shows the potential of the method as a simple design tool

Factors affecting breeding distribution of Storm-petrels <i>Hydrobates pelagicus</i> in Orkney and Shetland Capsule The main factors are past and present human activities, especially the introduction of rats to islands

Aims: To assess factors that influence breeding distribution and abundance of Storm-petrel. Methods: We used a database for 142 islands in Shetland and Orkney. Breeding status of Storm-petrel was related to data for each island on introduced and indigenous predators, other human-related features, and aspects of island geography. Results: Although 92% of the total land area of the archipelagos comprised islands with rats present, Storm-petrel colonies were almost totally restricted to rat-free islands. They also occurred more frequently on islands with cliffs, far from neighbouring islands with humans, and on islands with a low rate of human visits. Colony size was smaller on the smallest occupied islands. Breeding numbers of Great Skuas Stercorarius skua, Great Black-backed Gulls Larus marinus, and Storm-petrels all correlated, as each increased with island size. Conclusions The presence or absence of rats is the single most important influence on Storm-petrel breeding distribution in Orkney and Shetland. However, geographical and human-related effects, such as the presence of cliffs or the occurrence of human visits, also appear to influence the distribution of Storm-petrels, whereas avian predators appear to have had little effect until now