PubMed Health⌕ Search

PubMed · 12445773

RNA-catalyzed thioester synthesis.

Abstract

A series of efficient ribozymes with thioester synthetase activities have been isolated from CoA-linked RNA libraries containing four different lengths (30N, 60N, 100N, and 140N) of random nucleotide regions. Competitive evolution of these size-heterogeneous CoA-RNA libraries resulted in an RNA size population in the order of 30N > 60N >> 100N > 140N. From isolated clones in the 30N and 60N size groups, two predominant RNA sequences, TES1 (30N) and TES33 (60N), have been shown to catalyze the synthesis of different thioesters using various acyl adenylates as the substrates. Together with our previous findings, the current results demonstrate a CoA thioester synthetic pathway catalyzed by individual metabolic ribozymes, and suggest a likely mechanism for thioester synthesis and utilization in an RNA world.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Tricia M Coleman, Faqing Huang. 2002. RNA-catalyzed thioester synthesis.. https://doi.org/10.1016/s1074-5521(02)00264-8

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Complexation of fatty acids and fatty acid-CoAs with synthetic O-methylated polysaccharides.

An experimentally simple, but highly reproducible and reliable method has been developed to follow the complexation event of fatty acid (FA) and FA-CoA with polysaccharides. This method was based on the recent discovery of the unique blue-shifted UV absorption associated with the aggregation of tetraenoic fatty acids (TE-FAs) in aqueous solution. Complexation was monitored by recording the intensity of UV absorption at 250 nm ([free TE-FA]) and 303 nm ([complexed TE-FA]), and the K aggregate of C(20) t,t,t,t-TE-FA exhibited the ideal property for this purpose. Synthetic 3-O-methyl-D-mannose- and 6-O-methyl-D-glucose-containing lipopolysaccharides were found to exhibit a broad range of the binding affinities with C(20) t,t,t,t-TE-FAs as well as saturated FAs/FA-CoAs.

Acyl Coenzyme A↗

Neurodegeneration in autoimmune demyelination: recent mechanistic insights reveal novel therapeutic targets.

Multiple sclerosis (MS) is the most common chronic demyelinating disease of the central nervous system (CNS) and the major cause of neurological disability in young adults in Western countries. In spite of intensive research efforts, treatment options established to date do not sufficiently prevent the accumulation of tissue damage and clinical disability in patients with MS. We here describe recently identified molecules responsible for the inflammatory and the neurodegenerative processes in MS and its animal model, experimental autoimmune encephalomyelitis (EAE), and review new treatment options targeting both aspects of this disease.

Acyl Coenzyme A↗

High resolution crystal structures of unliganded and liganded human liver ACBP reveal a new mode of binding for the acyl-CoA ligand.

The acyl-CoA binding protein (ACBP) is essential for the fatty acid metabolism, membrane structure, membrane fusion, and ceramide synthesis. Here high resolution crystal structures of human cytosolic liver ACBP, unliganded and liganded with a physiological ligand, myristoyl-CoA are described. The binding of the acyl-CoA molecule induces only few structural differences near the binding pocket. The crystal form of the liganded ACBP, which has two ACBP molecules in the asymmetric unit, shows that in human ACBP the same acyl-CoA binding pocket is present as previously described for the bovine and Plasmodium falciparum ACBP and the mode of binding of the 3'-phosphate-AMP moiety is conserved. Unexpectedly, in one of the acyl-CoA binding pockets the acyl moiety is bound in a reversed mode as compared with the bovine and P. falciparum structures. In this binding mode, the myristoyl-CoA molecule is fully ordered and bound across the two ACBP molecules of the crystallographic asymmetric unit: the 3'-phosphate-AMP moiety is bound in the binding pocket of one ACBP molecule and the acyl chain is bound in the pocket of the other ACBP molecule. The remaining binding pocket cavities of these two ACBP molecules are filled by other ligand fragments. This novel binding mode shows that the acyl moiety can flip out of its classical binding pocket and bind elsewhere, suggesting a mechanism for the acyl-CoA transfer between ACBP and the active site of a target enzyme. This mechanism is of possible relevance for the in vivo function of ACBP.

Acyl Coenzyme A↗