Study of molecular cloning,purification and characterization of C.elegans Phosphodiesterase 3 (CEPDE3)isoforms.

Monday, September 22, 2014 — Poster Session II
4:00 p.m. – 6:00 p.m.	FAES Academic Center	NHLBI	MOLBIO-14

* FARE Award Winner

Authors

• S.G. Naik
• A. Samidurai
• D.K. Rhee
• F. Ahmad
• S.C. Hochman.
• N. Carter
• V.C. Manganiello.

Abstract

Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that regulate cellular levels of the second messengers; cAMP and cGMP by controlling their rates of degradation. There are 11 different PDE families, each with different isoforms and splice variants. Caenorhabditis elegans represents a unique model used extensively to study regulatory genes and their functional characterization. Our studies on C.elegans cyclic nucleotide phosphodiesterase 3(CEPDE3) gene demonstrated that the CEPDE3 gene is a homolog of the mammalian PDE3 family. The CEPDE3 gene is present on chromosome II, spanning about 22.2kb, encodes two different CEPDE3 isoforms ; CEPDE3 – LF(Long form) consists of 11 exons and codes for a 63.5 kDa protein; CEPDE3- SF( short form) has 8 exons and codes for a 54.2 kDa protein. Both isoforms contain the HD metal binding motif which is unique to the PDE superfamily. The predicted sequences of these isoforms show an overall 97% homology, with identical catalytic domains. Purification of CEPDE3- isoforms would enable us to characterize their catalytic properties , inhibitor specificities and sensitivities. Most importantly, it would allow us to determine its crystal structure and hopefully identify critical structural elements in the PDE3 catalytic pocket and aid in the design of specific and effective PDE3 inhibitors.

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