1SOJ

CATALYTIC DOMAIN OF HUMAN PHOSPHODIESTERASE 3B IN COMPLEX WITH IBMX

Summary for 1SOJ

• Entry DOI: 10.2210/pdb1soj/pdb
• Related: 1SO2
• Descriptor: cGMP-inhibited 3',5'-cyclic phosphodiesterase B, MAGNESIUM ION, 3-ISOBUTYL-1-METHYLXANTHINE, ... (4 entities in total)
• Functional Keywords: pde3b phosphodiesterase, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Multi-pass membrane protein (Potential): Q13370
• Total number of polymer chains: 12
• Total formula weight: 581155.62

Authors

Scapin, G.,Patel, S.B.,Chung, C.,Varnerin, J.P.,Edmondson, S.D.,Mastracchio, A.,Parmee, E.R.,Becker, J.W.,Singh, S.B.,Van Der Ploeg, L.H.,Tota, M.R. (deposition date: 2004-03-15, release date: 2004-05-11, Last modification date: 2023-08-23)

Primary citation

Scapin, G.,Patel, S.B.,Chung, C.,Varnerin, J.P.,Edmondson, S.D.,Mastracchio, A.,Parmee, E.R.,Singh, S.B.,Becker, J.W.,Van Der Ploeg, L.H.,Tota, M.R.
Crystal Structure of Human Phosphodiesterase 3B: Atomic Basis for Substrate and Inhibitor Specificity
Biochemistry, 43:6091-6100, 2004

PubMed Abstract: Phosphodiesterases (PDEs) are enzymes that modulate cyclic nucleotide signaling and as such are clinical targets for a range of disorders including congestive heart failure, erectile dysfunction, and inflammation. The PDE3 family comprises two highly homologous subtypes expressed in different tissues, and inhibitors of this family have been shown to increase lipolysis in adipocytes. A specific PDE3B (the lipocyte-localized subtype) inhibitor would be a very useful tool to evaluate the effects of PDE3 inhibition on lipolysis and metabolic rate and might become a novel tool for treatment of obesity. We report here the three-dimensional structures of the catalytic domain of human PDE3B in complex with a generic PDE inhibitor and a novel PDE3 selective inhibitor. These structures explain the dual cAMP/cGMP binding capabilities of PDE3, provide the molecular basis for inhibitor specificity, and can supply a valid platform for the design of improved compounds.

PubMed: 15147193
DOI: 10.1021/bi049868i

Experimental method

X-RAY DIFFRACTION (2.9 Å)