Publications by authors named "Corey R Mandel"

4 Publications

  • Page 1 of 1

Crystal structure of human mitochondrial acyl-CoA thioesterase (ACOT2).

Biochem Biophys Res Commun 2009 Aug 2;385(4):630-3. Epub 2009 Jun 2.

Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

Acyl-CoA thioesterases (ACOTs) catalyze the hydrolysis of CoA esters to free CoA and carboxylic acids and have important functions in lipid metabolism and other cellular processes. Type I ACOTs are found only in animals and contain an alpha/beta hydrolase domain, through currently no structural information is available on any of these enzymes. We report here the crystal structure at 2.1A resolution of human mitochondrial ACOT2, a type I enzyme. The structure contains two domains, N and C domains. The C domain has the alpha/beta hydrolase fold, with the catalytic triad Ser294-His422-Asp388. The N domain contains a seven-stranded beta-sandwich, which has some distant structural homologs in other proteins. The active site is located in a large pocket at the interface between the two domains. The structural information has significant relevance for other type I ACOTs and related enzymes.
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http://dx.doi.org/10.1016/j.bbrc.2009.05.122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731550PMC
August 2009

How to get all "A"s in polyadenylation.

Structure 2007 Sep;15(9):1024-6

In an elegant study in this issue of Structure, Balbo and Bohm (2007) report the crystal structure of yeast poly(A) polymerase in a ternary complex with its substrate MgATP and the elongating poly(A) tail, providing molecular insights into the mechanism of polyadenylation.
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http://dx.doi.org/10.1016/j.str.2007.08.002DOI Listing
September 2007

Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.

Nature 2006 Dec 26;444(7121):953-6. Epub 2006 Nov 26.

Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

Most eukaryotic messenger RNA precursors (pre-mRNAs) undergo extensive maturational processing, including cleavage and polyadenylation at the 3'-end. Despite the characterization of many proteins that are required for the cleavage reaction, the identity of the endonuclease is not known. Recent analyses indicated that the 73-kDa subunit of cleavage and polyadenylation specificity factor (CPSF-73) might be the endonuclease for this and related reactions, although no direct data confirmed this. Here we report the crystal structures of human CPSF-73 at 2.1 A resolution, complexed with zinc ions and a sulphate that might mimic the phosphate group of the substrate, and the related yeast protein CPSF-100 (Ydh1) at 2.5 A resolution. Both CPSF-73 and CPSF-100 contain two domains, a metallo-beta-lactamase domain and a novel beta-CASP (named for metallo-beta-lactamase, CPSF, Artemis, Snm1, Pso2) domain. The active site of CPSF-73, with two zinc ions, is located at the interface of the two domains. Purified recombinant CPSF-73 possesses RNA endonuclease activity, and mutations that disrupt zinc binding in the active site abolish this activity. Our studies provide the first direct experimental evidence that CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.
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http://dx.doi.org/10.1038/nature05363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866582PMC
December 2006

A serendipitous discovery that in situ proteolysis is essential for the crystallization of yeast CPSF-100 (Ydh1p).

Acta Crystallogr Sect F Struct Biol Cryst Commun 2006 Oct 30;62(Pt 10):1041-5. Epub 2006 Sep 30.

Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

The cleavage and polyadenylation specificity factor (CPSF) complex is required for the cleavage and polyadenylation of the 3'-end of messenger RNA precursors in eukaryotes. During structural studies of the 100 kDa subunit (CPSF-100, Ydh1p) of the yeast CPSF complex, it was serendipitously discovered that a solution that is infected by a fungus (subsequently identified as Penicillium) is crucial for the crystallization of this protein. Further analyses suggest that the protein has undergone partial proteolysis during crystallization, resulting in the deletion of an internal segment of about 200 highly charged and hydrophilic residues, very likely catalyzed by a protease secreted by the fungus. With the removal of this segment, yeast CPSF-100 (Ydh1p) has greatly reduced solubility and can be crystallized in the presence of a minute amount of precipitant.
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http://dx.doi.org/10.1107/S1744309106038152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2225192PMC
October 2006
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