更新于：2024-11-01

分支菌酸合酶

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与分支菌酸合酶相关的药物

S-004992

靶点

分支菌酸合酶

作用机制

分支菌酸合酶抑制剂

在研机构

南京长澳医药科技有限公司

原研机构

南京长澳医药科技有限公司

在研适应症

结核

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

EZ-120

靶点

结合分支杆菌抗原85 x 分支菌酸合酶

作用机制

结合分支杆菌抗原85抑制剂 [+1]

在研机构

Technische Universität München [+2]

原研机构

Technische Universität München

在研适应症

结核

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

KBF-611

靶点

分支菌酸合酶

作用机制

分支菌酸合酶抑制剂

在研机构-

原研机构

Shahid Beheshti University

在研适应症-

非在研适应症

结核

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与分支菌酸合酶相关的临床结果

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100 项与分支菌酸合酶相关的转化医学

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0 项与分支菌酸合酶相关的专利（医药）

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项与分支菌酸合酶相关的文献（医药）

2024-03-28·Microbial Genomics

Corrigendum: Lack of methoxy-mycolates characterizes the geographically restricted lineage 7 of Mycobacterium tuberculosis complex

Article

作者: Young, Douglas B ; Hailu, Elena ; Golby, Paul ; Adnew, Bethlehem ; Wheeler, Paul R ; Gagneux, Sebastien ; Gordon, Stephen V ; Comas, Iñaki ; Waddell, Simon J ; Cantillon, Daire ; Rose, Graham ; Aseffa, Abraham ; Larrouy-Maumus, Gerald ; Berg, Stefan ; Madrazo, Carlos

Lineage 7 (L7) emerged in the phylogeny of the Mycobacterium tuberculosis complex (MTBC) subsequent to the branching of 'ancient' lineage 1 and prior to the Eurasian dispersal of 'modern' lineages 2, 3 and 4.In contrast to the major MTBC lineages, the current epidemiol. suggests that prevalence of L7 is highly confined to the Ethiopian population, or when identified outside of Ethiopia, it has mainly been in patients of Ethiopian origin.To search for microbiol. factors that may contribute to its restricted distribution, we compared the genome of L7 to the genomes of globally dispersed MTBC lineages.The frequency of predicted functional mutations in L7 was similar to that documented in other lineages.These include mutations characteristic of modern lineages - such as constitutive expression of nitrate reductase - as well as mutations in the VirS locus that are commonly found in ancient lineages.We also identified and characterized multiple lineage-specific mutations in L7 in biosynthesis pathways of cell wall lipids, including confirmed deficiency of methoxy-mycolic acids due to a stop-gain mutation in the mmaA3 gene that encodes a methoxy-mycolic acid synthase.We show that the abolished biosynthesis of methoxy-mycolates of L7 alters the cell structure and colony morphol. on selected growth media and impacts biofilm formation.The loss of these mycolic acid moieties may change the host-pathogen dynamic for L7 isolates, explaining the limited geog. distribution of L7 and contributing to further understanding the spread of MTBC lineages across the globe.

2023-05-12·Microbial Genomics

Lack of methoxy-mycolates characterizes the geographically restricted lineage 7 of Mycobacterium tuberculosis complex

Article

作者: Hailu, Elena ; Golby, Paul ; Adnew, Bethlehem ; Wheeler, Paul R. ; Gordon, Stephen V. ; Gagneux, Sebastien ; Comas, Iñaki ; Young, Douglas B. ; Cantillon, Daire ; Rose, Graham ; Aseffa, Abraham ; Larrouy-Maumus, Gerald ; Waddell, Simon J. ; Berg, Stefan ; Madrazo, Carlos

Lineage 7 (L7) emerged in the phylogeny of the

Mycobacterium tuberculosis

complex (MTBC) subsequent to the branching of ‘ancient’ lineage 1 and prior to the Eurasian dispersal of ‘modern’ lineages 2, 3 and 4. In contrast to the major MTBC lineages, the current epidemiology suggests that prevalence of L7 is highly confined to the Ethiopian population, or when identified outside of Ethiopia, it has mainly been in patients of Ethiopian origin. To search for microbiological factors that may contribute to its restricted distribution, we compared the genome of L7 to the genomes of globally dispersed MTBC lineages. The frequency of predicted functional mutations in L7 was similar to that documented in other lineages. These include mutations characteristic of modern lineages – such as constitutive expression of nitrate reductase – as well as mutations in the VirS locus that are commonly found in ancient lineages. We also identified and characterized multiple lineage-specific mutations in L7 in biosynthesis pathways of cell wall lipids, including confirmed deficiency of methoxy-mycolic acids due to a stop-gain mutation in the mmaA3 gene that encodes a methoxy-mycolic acid synthase. We show that the abolished biosynthesis of methoxy-mycolates of L7 alters the cell structure and colony morphology on selected growth media and impacts biofilm formation. The loss of these mycolic acid moieties may change the host–pathogen dynamic for L7 isolates, explaining the limited geographical distribution of L7 and contributing to further understanding the spread of MTBC lineages across the globe.

2020-02-01·Molecular Microbiology2区 · 生物学

The mycolic acid reductase Rv2509 has distinct structural motifs and is essential for growth in slow‐growing mycobacteria

2区 · 生物学

Article

作者: Kalscheuer, Rainer ; Singh, Albel ; Hänisch, Milena ; Javid, Asma ; Bavro, Vassiliy N. ; Marshall, Robert L. ; Bhatt, Apoorva ; Cooper, Charlotte ; Schindler, Steffen

AbstractThe final step in mycolic acid biosynthesis in Mycobacterium tuberculosis is catalysed by mycolyl reductase encoded by the Rv2509 gene. Sequence analysis and homology modelling indicate that Rv2509 belongs to the short‐chain fatty acid dehydrogenase/reductase (SDR) family, but with some distinct features that warrant its classification as belonging to a novel family of short‐chain dehydrogenases. In particular, the predicted structure revealed a unique α‐helical C‐terminal region which we demonstrated to be essential for Rv2509 function, though this region did not seem to play any role in protein stabilisation or oligomerisation. We also show that unlike the M. smegmatis homologue which was not essential for growth, Rv2509 was an essential gene in slow‐growing mycobacteria. A knockdown strain of the BCG2529 gene, the Rv2509 homologue in Mycobacterium bovis BCG, was unable to grow following the conditional depletion of BCG2529. This conditional depletion also led to a reduction of mature mycolic acid production and accumulation of intermediates derived from 3‐oxo‐mycolate precursors. Our studies demonstrate novel features of the mycolyl reductase Rv2509 and outline its role in mycobacterial growth, highlighting its potential as a new target for therapies.