Structural basis for the bifunctionality of fructose-1,6-bisphosphate aldolase/phosphatase

Enzymes catalyse specific reactions and are essential for maintaining life. Although some are referred to as being bifunctional, they consist of either two distinct catalytic domains or a single domain that displays promiscuous substrate specificity. Thus, one enzyme active site is generally responsible for one biochemical reaction. In contrast to this conventional concept, archaeal fructose-1,6-bisphosphate (FBP) aldolase/phosphatase (FBPA/P) consists of a single catalytic domain, but catalyses two chemically distinct reactions of gluconeogenesis: (1) the reversible aldol condensation of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GA3P) to FBP; (2) the dephosphorylation of FBP to fructose-6-phosphate (F6P). Thus, FBPA/P is fundamentally different from ordinary enzymes whose active sites are responsible for a specific reaction. However, the molecular mechanism by which FBPA/P achieves its unusual bifunctionality remains unknown. Here we report the crystal structure of FBPA/P at 1.5-? resolution in the aldolase form, where a critical lysine residue forms a Schiff base with DHAP. A structural comparison of the aldolase form with a previously determined phosphatase form revealed a dramatic conformational change in the active site, demonstrating that FBPA/P metamorphoses its active-site architecture to exhibit dual activities. Thus, our findings expand the conventional concept that one enzyme catalyses one biochemical reaction.     

Bifidobacteria can protect from enteropathogenic infection through production of acetate

The human gut is colonized with a wide variety of microorganisms, including species, such as those belonging to the bacterial genus Bifidobacterium, that have beneficial effects on human physiology and pathology. Among the most distinctive benefits of bifidobacteria are modulation of host defence responses and protection against infectious diseases. Nevertheless, the molecular mechanisms underlying these effects have barely been elucidated. To investigate these mechanisms, we used mice associated with certain bifidobacterial strains and a simplified model of lethal infection with enterohaemorrhagic Escherichia coli O157:H7, together with an integrated 'omics' approach. Here we show that genes encoding an ATP-binding-cassette-type carbohydrate transporter present in certain bifidobacteria contribute to protecting mice against death induced by E. coli O157:H7. We found that this effect can be attributed, at least in part, to increased production of acetate and that translocation of the E. coli O157:H7 Shiga toxin from the gut lumen to the blood was inhibited. We propose that acetate produced by protective bifidobacteria improves intestinal defence mediated by epithelial cells and thereby protects the host against lethal infection.     

Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency. Using genome-wide linkage mapping and a positional candidate approach, we determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), are responsible for SIOD. Through analysis of data from persons with SIOD in 26 unrelated families, we observed that affected individuals from 13 of 23 families with severe disease had two alleles with nonsense, frameshift or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicate that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease.     

TRIC channels are essential for Ca2+ handling in intracellular stores

Cell signalling requires efficient Ca2+ mobilization from intracellular stores through Ca2+ release channels, as well as predicted counter-movement of ions across the sarcoplasmic/endoplasmic reticulum membrane to balance the transient negative potential generated by Ca2+ release. Ca2+ release channels were cloned more than 15 years ago, whereas the molecular identity of putative counter-ion channels remains unknown. Here we report two TRIC (trimeric intracellular cation) channel subtypes that are differentially expressed on intracellular stores in animal cell types. TRIC subtypes contain three proposed transmembrane segments, and form homo-trimers with a bullet-like structure. Electrophysiological measurements with purified TRIC preparations identify a monovalent cation-selective channel. In TRIC-knockout mice suffering embryonic cardiac failure, mutant cardiac myocytes show severe dysfunction in intracellular Ca2+ handling. The TRIC-deficient skeletal muscle sarcoplasmic reticulum shows reduced K+ permeability, as well as altered Ca2+ 'spark' signalling and voltage-induced Ca2+ release. Therefore, TRIC channels are likely to act as counter-ion channels that function in synchronization with Ca2+ release from intracellular stores.     

优美叶枝豆荚软珊瑚中的多羟基甾醇和神经酰胺

首次对优美叶枝豆荚软珊瑚Lobophytum delectum的次生代谢产物进行了研究并分离鉴定出3个多羟基甾醇和1个神经酰胺。通过波谱分析、化学降解及物理常数对照等方法鉴定出它们的化学结构分别为:(24S)-麦角甾-1β,3β,5α,6β-四醇(1)、(24S)-麦角甾-3β,5α,6β,25-四醇-25-单乙酸酯(2)、(24S)-麦角甾-5-烯-3β,25-二醇(3)和N-正十六碳酰基-正十八碳-4(E),8(E)-二烯鞘胺醇(4),首次发现(1)对MgC-803(人胃癌细胞)和Cne-1(人鼻咽癌细胞)有强抑制活性,IC50值分别为1.48和1.12μg/mL。     

听音室立体声重放系统中IACC的分布

在日本家庭中，听音室非常受欢迎．人们在自己的起居室中安装了优质的音响系统，用以欣赏音乐．最近，许多公司推出了很多有架子的音响系统设备，以方便人们放置喇叭和音响系统．但是大多数日本人都不知道如何将起居室改造成听音室．双耳互相关系数（IACC）是评价声场的重要参量，低的IACC值会带给人更好的音乐享受．文中探讨了现有房间中立体声重放系统的IACC分布．     

银离子络合萃取法及其在分离鱼油活性成分中的应用

进行了银离子络合萃取典型不饱和有机物一般规律研究 得出 ,当有机物的碳原子数与所含双键数 (或大π键数 )之比小于等于 6且没有空间位阻时 ,络合萃取可能进行 ;采用该络合法进行了高纯度浓缩鱼油中活性成分的研究 络合反应条件为 :硝酸银水溶液浓度4mol/L ,原料鱼油脂肪酸乙酯中活性成分含量 2 8% ,反应温度室温 ,反应 4h 络合后用升温及加水稀释法从水相中分离出被络合物 浓缩后活性成分含量达 90 %以上 ,回收率约 80 %