Browsing by Author "Yan, Juqiang (TTU)"
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Item ANKYRIN REPEAT-CONTAINING PROTEIN 2A Is an essential molecular chaperone for peroxisomal membrane-bound ASCORBATE PEROXIDASE3 in Arabidopsis(2010) Shen, Guoxin (TTU); Kuppu, Sundaram (TTU); Venkataramani, Sujatha (TTU); Wang, Jing (TTU); Yan, Juqiang (TTU); Qiu, Xiaoyun (TTU); Zhang, Hong (TTU)Arabidopsis thaliana ANKYRIN REPEAT-CONTAINING PROTEIN 2A (AKR2A) interacts with peroxisomal membrane-bound ASCORBATE PEROXIDASE3 (APX3). This interaction involves the C-terminal sequence of APX3 (i.e., a transmembrane domain plus a few basic amino acid residues). The specificity of the AKR2A-APX3 interaction suggests that AKR2A may function as a molecular chaperone for APX3 because binding of AKR2A to the transmembrane domain can prevent APX3 from forming aggregates after translation. Analysis of three akr2a mutants indicates that these mutant plants have reduced steady state levels of APX3. Reduced expression of AKR2A using RNA interference also leads to reduced steady state levels of APX3 and reduced targeting of APX3 to peroxisomes in plant cells. Since AKR2A also binds specifically to the chloroplast OUTER ENVELOPE PROTEIN7 (OEP7) and is required for the biogenesis of OEP7, AKR2A may serve as a molecular chaperone for OEP7 as well. The pleiotropic phenotype of akr2a mutants indicates that AKR2A plays many important roles in plant cellular metabolism and is essential for plant growth and development. © 2010 American Society of Plant Biologists.Item Steroidal antibiotics are antimetabolites of Acanthamoeba steroidogenesis with phylogenetic implications(2019) Zhou, Wenxu (TTU); Ramos, Emilio (TTU); Zhu, Xunlu (TTU); Fisher, Paxtyn M. (TTU); Kidane, Medhanie E. (TTU); Vanderloop, Boden H. (TTU); Thomas, Crista D. (TTU); Yan, Juqiang (TTU); Singha, Ujjal; Chaudhuri, Minu; Nagel, Michael T. (TTU); David Nes, W. (TTU)Pathogenic organisms may be sensitive to inhibitors of sterol biosynthesis, which carry antimetabolite properties, through manipulation of the key enzyme, sterol methyltransferase (SMT). Here, we isolated natural suicide substrates of the ergosterol biosynthesis pathway, cholesta-5,7,22,24-tetraenol (CHT) and ergosta-5,7,22,24(28)-tetraenol (ERGT), and demonstrated their interference in Acanthamoeba castellanii steroidogenesis: CHT and ERGT inhibit trophozoite growth (EC50 of 51 nM) without affecting cultured human cell growth. Washout experiments confirmed that the target for vulnerability was SMT. Chemical, kinetic, and protein-binding studies of inhibitors assayed with 24-AcSMT [catalyzing C28-sterol via 24(28)-olefin production] and 28-AcSMT [catalyzing C29-sterol via 25(27)-olefin production] revealed interrupted partitioning and irreversible complex formation from the conjugated double bond system in the side chain of either analog, particularly with 28-AcSMT. Replacement of active site Tyr62 with Phe or Leu residues involved in cation- interactions that model product specificity prevented protein inactivation. The alkylating properties and high selective index of 103 for CHT and ERGT against 28-AcSMT are indicative of a new class of steroidal antibiotic that, as an antimetabolite, can limit sterol expansion across phylogeny and provide a novel scaffold in the design of amoebicidal drugs. Animal studies of these suicide substrates can further explore the potential of their antibiotic properties.