Sphingosine-1-phosphate metabolism: A structural perspective.
Sphingolipids represent an important class of bioactive signaling lipids which have key roles in numerous cellular processes. Over the last few decades, the levels of bioactive sphingolipids and/or their metabolizing enzymes have been realized to be important factors involved in disease development and progression, most notably in cancer. Targeting sphingolipid-metabolizing enzymes in disease states has been the focus of many studies and has resulted in a number of pharmacological inhibitors, with some making it into the clinic as therapeutics. In order to better understand the regulation of sphingolipid-metabolizing enzymes as well as to develop much more potent and specific inhibitors, the field of sphingolipids has recently taken a turn toward structural biology. The last decade has seen the structural determination of a number of sphingolipid enzymes and effector proteins. In these terms, one of the most complete arms of the sphingolipid pathway is the sphingosine-1-phosphate (S1P) arm. The structures of proteins involved in the function and regulation of S1P are being used to investigate further the regulation of said proteins as well as in the design and development of inhibitors as potential therapeutics.
a Department of Pharmacological Sciences and.
Michael J
MJ
Pulkoski-Gross
b Department of Medicine , Stony Brook University , Stony Brook , NY , USA .|c Stony Brook Cancer Center , Stony Brook , NY , USA , and.
Jane C
JC
Donaldson
b Department of Medicine , Stony Brook University , Stony Brook , NY , USA .|c Stony Brook Cancer Center , Stony Brook , NY , USA , and.|d Northport Veterans Affairs Medical Center , Northport , NY , USA.
Lina M
LM
Obeid
D000446:Aldehyde-Lyases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism*; D049990:Membrane Transport Modulators; D008958:Models, Molecular; D008968:Molecular Conformation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015290:Second Messenger Systems; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors; D000099157:Sphingosine Kinase
D000446:Aldehyde-Lyases; D004791:Enzyme Inhibitors; D008024:Ligands; D008246:Lysophospholipids; D049990:Membrane Transport Modulators; D017853:Phosphotransferases (Alcohol Group Acceptor); D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000081025:Sphingosine-1-Phosphate Receptors; D000099157:Sphingosine Kinase; C477362:S1PR1 protein, human; C060506:sphingosine 1-phosphate; C000594250:sphingosine kinase 2, human; C022649:sphingosine 1-phosphate lyase (aldolase)
Sphingolipid metabolism; sphingosine kinases; sphingosine-1-phosphate; sphingosine-1-phosphate receptors; structural biology