抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.

/pdf/exploring-the-full-spectrum-of-macrophage-activation-b5rnrcgcen.pdf

Exploring the full spectrum of macrophage activation.

The small-molecule topology generator PRODRG is described, which takes input from existing coordinates or various two-dimensional formats and automatically generates coordinates and molecular topologies suitable for X-ray refinement of protein–ligand complexes. Test results are described for automatic generation of topologies followed by energy minimization for a subset of compounds from the Cambridge Structural Database, which shows that, within the limits of the empirical GROMOS87 force field used, structures with good geometries are generated. X-ray refinement in X-­PLOR/CNS, REFMAC and SHELX using PRODRG-generated topologies produces results comparable to refinement with topologies from the standard libraries. However, tests with distorted starting coordinates show that PRODRG topologies perform better, both in terms of ligand geometry and of crystallographic R factors.

/pdf/prodrg-a-tool-for-high-throughput-crystallography-of-protein-2o0obb3hfy.pdf

PRODRG: a tool for high-throughput crystallography of protein–ligand complexes

Pretreatment technologies are aimed to increase enzyme accessibility to biomass and yields of fermentable sugars. In general, pretreatment methods fall into four different categories including physical, chemical, physico-chemical, and biological. This paper comprehensively reviews the lignocellulosic wastes to bioethanol process with a focus on pretreatment methods, their mechanisms, advantages and disadvantages as well as the combinations of different pretreatment technologies. Moreover, the new advances in plant “omics” and genetic engineering approaches to increase cellulose composition, reduce cellulose crystallinity, produce hydrolases and protein modules disrupting plant cell wall substrates, and modify lignin structure in plants have also been expansively presented.

Lignocellulosic biomass to bioethanol, a comprehensive review with a focus on pretreatment

Efficient enzymatic conversion of crystalline polysaccharides is crucial for an economically and environmentally sustainable bioeconomy but remains unfavorably inefficient. We describe an enzyme that acts on the surface of crystalline chitin, where it introduces chain breaks and generates oxidized chain ends, thus promoting further degradation by chitinases. This enzymatic activity was discovered and further characterized by using mass spectrometry and chromatographic separation methods to detect oxidized products generated in the absence or presence of H 2 18 O or 18 O 2 . There are strong indications that similar enzymes exist that work on cellulose. Our findings not only demonstrate the existence of a hitherto unknown enzyme activity but also provide new avenues toward more efficient enzymatic conversion of biomass.

https://science.sciencemag.org/content/sci/330/6001/219.full.pdf

An oxidative enzyme boosting the enzymatic conversion of recalcitrant polysaccharides.

https://www.pure.ed.ac.uk/ws/files/23418057/Identification_and_activity_of_inhibitors_of_the_essential.pdf

Identification and activity of inhibitors of the essential nematode-specific metalloprotease DPY-31

Cyclodipeptide synthases (CDPSs) produce a variety of cyclic dipeptide products by utilising two aminoacylated tRNA substrates. We sought to investigate the minimal requirements for substrate usage in this class of enzymes as the relationship between CDPSs and their substrates remains elusive. Here, we investigated the Bacillus thermoamylovorans enzyme, BtCDPS, which synthesises cyclo(l-Leu-l-Leu). We systematically tested where specificity arises and, in the process, uncovered small molecules (activated amino esters) that will suffice as substrates, although catalytically poor. We solved the structure of BtCDPS to 1.7 A and combining crystallography, enzymatic assays and substrate docking experiments propose a model for how the minimal substrates interact with the enzyme. This work is the first report of a CDPS enzyme utilizing a molecule other than aa-tRNA as a substrate; providing insights into substrate requirements and setting the stage for the design of improved simpler substrates.

/pdf/bypassing-the-requirement-for-aminoacyl-trna-by-a-3ovqus8j3p.pdf

Bypassing the requirement for aminoacyl-tRNA by a cyclodipeptide synthase enzyme

Ligand-induced signalling and conformational change of the 39 kD glycoprotein from human articular chondrocytes

Fatty-acylation target sequence in the ligand-binding domain of vertebrate steroid receptors demarcates evolution from estrogen-related receptors.

The recent work on a variety of family 18 chitonolytic enzymes has yielded important data concerning the structure, substrate-binding, catalysis, inhibitor-binding and even dynamics. These data have been useful in helping to better understand the roles of various types of chitinases in chitin hydrolysis, to rationally engineer the properties of these enzymes, thus making them more suitable as biocatalysts, and to study and understand the effectiveness of natural and designed chitinase inhibitors, which may be of medical interest. On the other hand, the recent work on ChiB shows that catalysis in family 18 chitinases is a highly complicated process, involving larger parts of the enzyme and dynamics. Thus, despite recent discoveries, there is still a lot more to discover about how these enzyme work.

Douglas R. Houston

Papers

Identification and activity of inhibitors of the essential nematode-specific metalloprotease DPY-31

Bypassing the requirement for aminoacyl-tRNA by a cyclodipeptide synthase enzyme

Ligand-induced signalling and conformational change of the 39 kD glycoprotein from human articular chondrocytes

Fatty-acylation target sequence in the ligand-binding domain of vertebrate steroid receptors demarcates evolution from estrogen-related receptors.

Structure and function of chitinolytic enzymes