Structural Biology Research Papers - Academia.edu (original) (raw)

Aspergillus fumigatus is an opportunistic mold responsible for severe life-threatening fungal infections in immunocompromised patients. The cell wall, an essential structure composed of glucan, chitin, and galactomannan, is considered to... more

Aspergillus fumigatus is an opportunistic mold responsible for severe life-threatening
fungal infections in immunocompromised patients. The cell wall, an essential
structure composed of glucan, chitin, and galactomannan, is considered to be a
target for the development of antifungal drugs. The nucleotide sugar donor GDP-mannose
(GDP-Man)
is required for the biosynthesis of galactomannan, glycosylphosphatidylinositol
(GPI) anchors, glycolipid, and protein glycosylation. Starting
from fructose-6-
phosphate,
GDP-Man
is produced by the sequential action of the
enzymes phosphomannose isomerase, phosphomannomutase (Pmm), and GDP-mannose
pyrophosphorylase. Here, using heterokaryon rescue and gene knockdown
approaches we demonstrate that the phosphomannomutase encoding gene in A. fumigatus
(pmmA) is essential for survival. Reduced expression of pmmA is associated
with significant morphological defects including retarded germination, growth, reduced
conidiation, and abnormal polarity. Moreover, the knockdown strain exhibited
an altered cell wall organization and sensitivity toward cell wall perturbing agents. By
solving the first crystal structure of A. fumigatus phosphomannomutase (AfPmmA)
we identified non-conservative
substitutions near the active site when compared to
the human orthologues. Taken together, this work provides a genetic and structural
foundation for the exploitation of AfPmmA as a potential antifungal target.

The exoskeleton of the lobster Homarus americanus is a multiphase biological composite material which consists of an organic matrix (crystalline α-chitin fibers and various types of non-crystalline proteins) and minerals (mainly calcite).... more

The exoskeleton of the lobster Homarus americanus is a multiphase biological composite material which consists of an organic matrix (crystalline α-chitin fibers and various types of non-crystalline proteins) and minerals (mainly calcite). In this study we discuss experimental data about the mesoscopic structure and the crystallographic texture (orientation distribution) of the α-chitin–protein fiber network in this material. The synchrotron measurements reveal very strong crystallographic textures of the α-chitin. According to these data, a large fraction of the α-chitin lattice cells is arranged with their longest axis parallel to the normal of the surface of the exoskeleton. Additionally, a smaller fraction of the α-chitin cells is oriented with their longest axis perpendicular to the cuticle surface. These structural investigations reveal the pronounced role of crystallographic orientation distributions in mineralized biological composite materials which may be of relevance for an improved understanding of biological and bio-inspired nano-composites.

The insulin receptor (IR) is a four-chain, transmembrane dimer held together by disulfide bonds. To gain information about the molecular envelope and the organization of its domains, single-molecule images of the IR ectodomain and its... more

The insulin receptor (IR) is a four-chain, transmembrane dimer held together by disulfide bonds. To gain information about the molecular envelope and the organization of its domains, single-molecule images of the IR ectodomain and its complexes with three Fabs have been analyzed by electron microscopy. The data indicate that the IR ectodomain resembles a U-shaped prism of approximate dimensions 90

This paper reports the results of the first dynamic labeling experiment with regenerating spines of sea urchins Paracentrotus lividus using the stable isotope 26Mg and NanoSIMS high-resolution isotopic imaging, which provide a direct... more

This paper reports the results of the first dynamic labeling experiment with regenerating spines of sea urchins Paracentrotus lividus using the stable isotope 26Mg and NanoSIMS high-resolution isotopic imaging, which provide a direct information about the growth process. Growing spines were labeled twice (for 72 and 24 h, respectively) by increasing the abundance of 26Mg in seawater. The incorporation of 26Mg into the growing spines was subsequently imaged with the NanoSIMS ion microprobe. Stereom trabeculae initially grow as conical micro-spines, which form within less than 1 day. These micro-spines fuse together by lateral outgrowths and form a thin, open meshwork (inner stereom), which is subsequently reinforced by addition of layered thickening deposits (outer stereom). The (longitudinal) growth rate of the inner stereom is ca. 125 μm/day. A single (ca. 1 μm) thickening layer in the stereom trabeculae is deposited during 24 h. The thickening process is contemporaneous with the formation micro-spines and involves both longitudinal trabeculae and transverse bridges to a similar degree. Furthermore, the skeleton-forming cells remain active in the previously formed open stereom for at least 10 days, and do not migrate upwards until the end of the thickening process. The experimental capability presented here provides a new way to obtain detailed information about the skeleton formation of a multitude of marine, calcite producing organisms.

Synopsis: The crystal structure of the synthetase domain of human CTPS has been determined. The structure is the first of an eukaryotic CTPS and provides a starting point for drug design towards CTPS. ... Synopsis: The crystal structure... more

Synopsis: The crystal structure of the synthetase domain of human CTPS has been determined. The structure is the first of an eukaryotic CTPS and provides a starting point for drug design towards CTPS. ... Synopsis: The crystal structure of human CA II has been determined in complex with two CA inhibitors (CAIs) containing conventional sulfonamide and thiadiazole moieties separated by a -CF 2 - or -CHNH 2 - spacer group. ... Synopsis: The structure of porcine pancreatic elastase at 1.5 Å resolution has a unique conformation induced by tris( ...

I was appalled when I read a report in Nature last year about proposals by the Indian government to encourage universities to teach astrology (Nature 411, 227; 200110.1038/35077282), but never thought that anything similar might occur in... more

I was appalled when I read a report in Nature last year about proposals by the Indian government to encourage universities to teach astrology (Nature 411, 227; 200110.1038/35077282), but never thought that anything similar might occur in the West. ... To read this story in full you ...