4v24

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Sphingosine kinase 1 in complex with PF-543

Structural highlights

4v24 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.8Å
Ligands:ACT, GYR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SPHK1_HUMAN Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo-dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol.[1]

Publication Abstract from PubMed

The most potent inhibitor of Sphingosine Kinase 1 (SPHK1) so far identified is PF-543. The crystal structure of SPHK1 in complex with inhibitor PF-543 to 1.8 A resolution reveals the inhibitor bound in a bent conformation analogous to that expected of a bound sphingosine substrate but with a rotated head group. The structural data presented will aid in the design of SPHK1 and SPHK2 inhibitors with improved properties.

Crystal Structure of Sphingosine Kinase 1 with PF-543.,Wang J, Knapp S, Pyne NJ, Pyne S, Elkins JM ACS Med Chem Lett. 2014 Oct 27;5(12):1329-33. doi: 10.1021/ml5004074. eCollection, 2014 Dec 11. PMID:25516793[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
13 reviews cite this structure
Sphingolipid metabolism in cancer signalling and therapy.
Ogretmen et al. (2018)
12 more
27 other articles
No citations found

See Also

References

  1. ↑ Alvarez SE, Harikumar KB, Hait NC, Allegood J, Strub GM, Kim EY, Maceyka M, Jiang H, Luo C, Kordula T, Milstien S, Spiegel S. Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature. 2010 Jun 24;465(7301):1084-8. doi: 10.1038/nature09128. PMID:20577214 doi:10.1038/nature09128
  2. ↑ Wang J, Knapp S, Pyne NJ, Pyne S, Elkins JM. Crystal Structure of Sphingosine Kinase 1 with PF-543. ACS Med Chem Lett. 2014 Oct 27;5(12):1329-33. doi: 10.1021/ml5004074. eCollection, 2014 Dec 11. PMID:25516793 doi:http://dx.doi.org/10.1021/ml5004074

Contents


PDB ID 4v24

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