Fusarium graminearum(sexual stage:Gibberella zeae)is the causative agent of Fusarium Head Blight(FHB),which is one of the most destructive plant disease of cereals,accounting for high grain yield losses,especially for wheat and maize.Like other fungal pathogens,several extracellular enzymes secreted by G.zeae are known to be involved in host infection.Among these secreted lipases,G.zeae lipase(GZEL),which is encoded by the FGL1 gene,was demonstrated to be crucial to G.zeae pathogenicity.However,the precise mechanism of GZEL remains unclear due to a lack of detailed structural information.In this study,we report the crystal structure of GZEL at the atomic level.The structure of GZEL displays distinct structural differences compared to reported homologues and indicates a unique“double lock”enzymatic mechanism.To gain insight into substrate/inhibitor recognition,we proposed a model of GZEL in complex with substrate and the lipase inhibitor ebelactone B(based on the reported structures of GZEL homologues),which defines possible substrate binding sites within the catalytic cleft and suggests an“anti sn-l”binding mode.These results pave the way to elucidating the mechanism of GZEL and thus provide clues for the design of anti-FHB inhibitors.
The importance of NAC(named as NAM,ATAF1,2,and CUC2)proteins in plant development,transcription regulation and regulatory pathways involving proteinprotein interactions has been increasingly recognized.We report here the high resolution crystal structure of SNAC1(stress-responsive NAC)NAC domain at 2.5Å.Although the structure of the SNAC1 NAC domain shares a structural similarity with the reported structure of the ANAC NAC1 domain,some key features,especially relating to two loop regions which potentially take the responsibility for DNA-binding,distinguish the SNAC1 NAC domain from other reported NAC structures.Moreover,the dimerization of the SNAC1 NAC domain is demonstrated by both soluble and crystalline conditions,suggesting this dimeric state should be conserved in this type of NAC family.Additionally,we discuss the possible NAC-DNA binding model according to the structure and reported biological evidences.
Mycobacterium tuberculosis,which belongs to the genus Mycobacterium,is the pathogenic agent for most tuberculosis(TB).As TB remains one of the most rampant infectious diseases,causing morbidity and death with emergence of multi-drug-resistant and extensively-drugresistant forms,it is urgent to identify new drugs with novel targets to ensure future therapeutic success.In this regards,the structural genomics of M.tuberculosis provides important information to identify potential targets,perform biochemical assays,determine crystal structures in complex with potential inhibitor(s),reveal the key sites/residues for biological activity,and thus validate drug targets and discover novel drugs.In this review,we will discuss the recent progress on novel targets for structure-based anti-M.tuberculosis drug discovery.
