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The complex structures of ALKBH2 mutants cross-linked to dsDNA reveal the conformational swing of β-hairpin

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Science China Chemistry 2014年第2期57卷 307-313页

作者： CHEN BaoEn gan jianhua YANG CaiGuang Shanghai Institute of Materia Medica Chinese Academy of Sciences School of Life Sciences Fudan University

Mammalian AlkB homologue 2(ALKBH2)is the primary housekeeping DNA demethylase,effectively repairing endogenously formed methylated lesions in double-stranded *** previous studies demonstrated that a hydrophobicβ-hairpin motif of ALKBH2 could play crucial roles in base-pair stability interrogation and damaged base *** chemical cross-linking strategy,we obtained two crystal structures of human ALKBH2 mutant bound to duplex *** structural analysis suggests that theβ-hairpin motif is flexible in conformation and is likely to slide along the DNA duplex in local regions to search for damaged *** study provides a new mechanistic insight into DNA damage detection by ALKBH2.

关键词： DNA repair ALKBH2 chemical cross-linking B-hairpin motif damage detection

Chemical and structural biology of nucleic acids and protein-nucleic acid complexes for novel drug discovery

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Science China Chemistry 2011年第1期54卷 3-23页

作者： gan jianhua SHENG Jia HUANG Zhen Department of Chemistry Georgia State UniversityAtlantaGA 30303USA

Since nucleic acids(DNA and RNA) play very important roles in cells,they are molecular targets of many clinically used drugs,such as anticancer drugs and *** of clinical demands for treating various deadly cancers and drug-resistant strains of pathogens,there are urgent needs to develop novel therapeutic *** nucleic acids hasn’t been the mainstream of drug discovery in the past,and the lack of 3D structural information for designing and developing drug specificity is one of the main ***,many important structures of nucleic acids and their protein complexes have been determined over the past decade,which provide novel platforms for future drug design and *** this review,we describe some useful nucleic acid structures,particularly their interactions with the ligands and therapeutic candidates or even *** summarize important information for designing novel potent drugs and for targeting nucleic acids and protein-nucleic acid complexes to treat cancers and overcome the drug-resistant problems.

关键词： nucleic acid targets DNA and RNA protein-nucleic acid complexes DNA duplex and junction G-quadruplex ribozyme riboswitch ribosome topoisomerase inhibitors antibiotics structure-based drug design therapeutic agents

A Peptide Binder of E3 Ligase Adaptor SPOP Disrupts Oncogenic SPOP-Protein Interactions in Kidney Cancer Cells

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Chinese Journal of Chemistry 2021年第2期39卷 274-280页

作者： Zhen Wang Hao Zhang Baoen Chen Sisheng Ouyang Tong Zheng Ran Zhou Ze Dong Yue Huang Tao Zhang Hualiang Jiang jianhua gan Cheng Luo Cai-Guang Yang School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjingJiangsu210023 China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203 China University of Chinese Academy of Sciences Beijing100049 China School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUCASHangzhouZhejiang310024 China Shanghai Institute for Advanced Immunochemical Studies ShanghaiTech UniversityShanghai201210 China School of Life Sciences Fudan UniversityShanghai200433 China

The E3 ligase adaptor SPOP,overexpressed in the nucleus but frequently dislocated into the cytoplasm in all clear cell Renal Cell Carcinomas(ccRCC),serves as a regulatory hub to promote kidney cancer through the ubiquitination and degradation of multiple downstream cancer ***,our identification of a selective small-molecule inhibitor of the SPOP-phosphatase and tensin homolog(PTEN)interaction has demonstrated that the oncogenic SPOP-protein interaction would be a druggable target specific to ccRCC *** our knowledge,this is the first time such a small-molecule inhibitor has been ***,we have identified a peptide binder for the SPOP-MATH domain that disrupts the oncogenic SPOP-protein interactions in kidney cancer *** design and biophysical characterization yielded peptide Pep38 that binds to the MATH domain of SPOP and competes on PTEN-binding to SPOP in *** X-ray complex structure reveals that the peptide binder features the following combination:one,a mimic of the native peptide binder and two,an additionalβ-strand motif in sequence,which could contribute to increased binding *** order to improve cellular permeability,we fused Pep38 with the delivery peptide TAT to prepare peptide TAT38,which inhibits the endogenous substrate binding to SPOP and suppresses the proliferation of the ccRCC *** identification of the peptide inhibitors for SPOP-protein interactions provides further validation that the oncogenic SPOP-signaling pathway in ccRCC could be a druggable target specifically applicable to the therapy of kidney cancers.

关键词： SPOP Protein-protein interaction Clear cell Renal Cell Carcinomas Crystal structure Peptide inhibitor

原核生物pre-tRNA 5'末端剪切酶的结构和功能研究

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复旦学报(自然科学版) 2025年第1期64卷 113-120页

作者：邵齐源李洋洋张威振甘建华复旦大学生命科学学院上海200438

5'末端的剪切是pre-tRNA加工和成熟过程中非常重要的一个环节,由RNase P负责催化。不同于常规的RNase P,原核生物中存在一类protein-only RNase P(也称HARP),不需要依赖核酶就能对pre-tRNA的5'末端进行剪切。为了阐明HARP结合和剪切pre-... 详细信息

5'末端的剪切是pre-tRNA加工和成熟过程中非常重要的一个环节,由RNase P负责催化。不同于常规的RNase P,原核生物中存在一类protein-only RNase P(也称HARP),不需要依赖核酶就能对pre-tRNA的5'末端进行剪切。为了阐明HARP结合和剪切pre-tRNA的分子机制,我们表达和纯化了Thermocrinis ruber来源的HARP蛋白(TrHARP)。定点突变、分子筛和体外活性实验证实TrHARP具有pre-tRNA剪切活性,而且该活性受到蛋白聚合状态的影响。此外,我们还筛选获得了TrHARP蛋白质的晶体,采集了衍射数据并建立了初始的结构模型。尽管TrHARP与Aquifex aeolicus来源的HARP Aq_880的折叠方式类似,但TrHARP与Aq_880在结构中的聚合方式和相对方位存在显著的差异。分子筛以及负染电镜实验结果均显示pre-tRNA的引入会导致HARP结构的解聚,这为进一步阐明HARP结合和催化pre-tRNA的5'末端成熟的分子机制奠定了基础。

关键词： protein-only RNase P pre-tRNA HARP 晶体结构功能蛋白表达

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铁坑褐铁矿选矿工艺研究

金属矿山 2006年第5期35卷 32-36页

作者：甘建华新余铁坑矿业有限责任公司

通过铁坑褐铁矿磨矿细度、强磁选、浮选、浮选中间产品选矿的试验,磨矿-强磁-再磨反浮选流程试验,磨矿-强磁-再磨强磁-反浮选流程试验和扩大连续选矿试验,制定了铁坑褐铁矿选矿的合理工艺流程,并确定磨矿-强磁选-再磨强磁选-反浮选工艺... 详细信息

通过铁坑褐铁矿磨矿细度、强磁选、浮选、浮选中间产品选矿的试验,磨矿-强磁-再磨反浮选流程试验,磨矿-强磁-再磨强磁-反浮选流程试验和扩大连续选矿试验,制定了铁坑褐铁矿选矿的合理工艺流程,并确定磨矿-强磁选-再磨强磁选-反浮选工艺为选厂工业设计推荐流程,较好地解决了褐铁矿选矿工艺问题。

关键词：褐铁矿强磁选再磨强磁选反浮选

Development of Water Resources

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Development of Water Resources

Histamine activates HinK to promote the virulence of Pseudomonas aeruginosa

作者： Wang Hao Wang jianhua gan Hong Zhang Haitao Yan Denghua Xiao Yuquan

＜正＞In recent years,breakthrough progress has been made in China in the fields of water resources research such as basic theories and evolutionary regulari- ties of water resources,macro-level water strategies,water...

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Science Bulletin 2021年第11期66卷 1101-1118,M0004页

作者： Yaya Wang Qiao Cao Qin Cao jianhua gan Ning Sun Cai-Guang Yang Taeok Bae Min Wu Lefu Lan State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China College of Life Science Northwest UniversityXi'an 710069China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Genetic Engineering Shanghai Public Health Clinical CenterCollaborative Innovation Center of Genetics and DevelopmentSchool of Life SciencesFudan UniversityShanghai 201438China The State Key Laboratory of Chemical Biology and Drug Discovery Department of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic UniversityHong Kong 999077China School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Department of Microbiology and Immunology Indiana University School of Medicine-NorthwestGary IN 46408USA Department of Biomedical Sciences University of North DakotaGrand Forks ND 58203-9037USA NMPA Key Laboratory for Testing Technology of Pharmaceutical Microbiology Shanghai Institute for Food and Drug ControlShanghai 201203China

During infections,bacteria stimulate host cells to produce and release histamine,which is a key mediator of vital cellular processes in ***,the mechanisms underlying the bacterial cell’s ability to sense and respond to histamine are poorly ***,we show that HinK,a Lys R-type transcriptional regulator,is required to evoke responses to histamine in Pseudomonas aeruginosa,an important human *** directly binds to and activates the promoter of genes involved in histamine uptake and metabolism,iron acquisition,and Pseudomonas quinolone signal(PQS)*** transcriptional regulatory activity of HinK is induced when histamine is present,and it occurs when HinK binds with imidazole-4-acetic acid(Im AA),a histamine metabolite whose production in *** depends on the HinK-activated histamine uptake and utilization operon hin ***,the inactivation of HinK inhibits diverse pathogenic phenotypes of *** results suggest that histamine acts as an interkingdom signal and provide insights into the mechanism used by pathogenic bacteria to exploit host regulatory signals to promote virulence.

关键词： Pseudomonas aeruginosa Histamine Metabolism Host-microbe interaction Virulence

大肠杆菌GhoS的纯化及X射线衍射分析（英文）

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复旦学报（自然科学版） 2018年第1期57卷 30-35页

作者：程云珊李继喜甘建华复旦大学生命科学学院生理学与生物物理学系上海200438

Toxin-antitoxin体系在细菌中发挥着许多关键性的作用.作为唯一的typeⅤTA系统的代表,GhoS能够剪切GhoT蛋白的mRNA,进而抑制GhoT的毒性.GhoS在溶液中有单体和二体两种不同的存在形式,而且两种形式均具有催化活性.尽管目前有一个GhoS的NM... 详细信息

Toxin-antitoxin体系在细菌中发挥着许多关键性的作用.作为唯一的typeⅤTA系统的代表,GhoS能够剪切GhoT蛋白的mRNA,进而抑制GhoT的毒性.GhoS在溶液中有单体和二体两种不同的存在形式,而且两种形式均具有催化活性.尽管目前有一个GhoS的NMR溶液结构已经报道,GhoS是如何二聚以及如何识别和降解底物的机制还不明确.本文中我们报道了GhoS F14A突变体的纯化和初步晶体学研究.GhoS晶体的衍射分辨率为1.5.晶体属于P21空间群,晶胞参数为a=51.0,b=37.3,c=52.3,α=90.0°,β=119.6°,γ=90.0°.晶体的溶剂含量为35%,每个不对称单元中含有两个蛋白分子.

关键词：毒素/抗毒素 GhoS mRNA切割干扰酶核酸内切酶

太阳能并网发电系统和风冷热泵一机三用机组及变负荷贮能系统在建筑上的运用

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墙材革新与建筑节能 2010年第1期 57-58页

作者：甘建华南昌市节能评估事务所南昌330035

我国能源供应日益紧缺,电力供应也严重不足。本文介绍太阳能并网发电系统和风冷热泵一机三用机组及变负荷贮能系统在建筑中的应用,以加快新能源、新技术的推广应用。

关键词：并网发电光伏电池组件热回收贮能器