Sphingosine kinase

The Sphingosine Kinase Type 1 (SphK1) structure reveals a two domain alpha-beta architecture. ^[1] The catalytic site (used in converting sphingosine to S1P-see below in "function" section for more details) is in a hydrophobic cleft, located between the two domains. ^[1] This hydrophobic cleft is an ideal binding pocket for a hydrophobic lipid, like sphingosine (an 18-carbon amino alcohol with an unsaturated hydrocarbon chain). ^[1]

Sphingolipids

Sphingolipids are a class of lipids, containing a sphingosine base moiety, essential for eukaryotic cell membrane structure and function. ^[2] Importantly, sphingolipids can additionally act as critical signaling molecules used in many eukaryotic homeostatic cellular processes, such as inflammation, proliferation, apoptosis, cell migration, and pathogen defense. ^[2] Because of this, it is critical for sphingolipids and their metabolizing enzymes to exist in a delicate homeostatic balance within the eukaryotic cell system.

Sphingosine-1-Phosphate (S1P), a lipid within the sphingolipid class, is an important signaling molecule that can participate in intracellular and extracellular signaling. ^{[2] [3]} If meant to be an intracellular signaling molecule, S1P is important for cell survival, growth, and overall cell function.^[3] Alternatively, if S1P is meant to be an extracellular signaling molecule, later binding to one of five different S1P G-Protein Coupled Receptors on the same or different cell type, it is used to activate many signaling cascades important for cell response. ^[3] One important function of S1P, whether its fate serves intracellularly or extracellularly, is eliciting the immune response (i.e. lymphocyte trafficking), especially as a mechanism in pathogen defense. ^[3]

Sphingosine Kinase (SphK1 and SphK2)

Sphingosine Kinase, existing in two isoenzyme forms, SphK1 and SphK2, creates S1P via the phosphorylation of sphingosine, the base moiety of all sphingolipids. ^[3] SphK1 is a central enzyme controlling the levels of S1P within the eukaryotic cell, and thus, is an important regulator of diverse cellular functions. ^[1]

Relevance

Structural highlights

Ligand Key: SQS: Sphingosine EDO: 1,2-ETHANEDIOL SO4: SULFATE ION