3nkr

From Proteopedia

Jump to: navigation, search

Crystal structure of mouse autotaxin in complex with 22:6-LPA

Structural highlights

3nkr is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.704Å
Ligands:BMA, CA, EDO, K, MAN, NA, NAG, NKR, SCN, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ENPP2_MOUSE Note=May contribute to obesity.

Function

ENPP2_MOUSE Hydrolyzes lysophospholipids to produce lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Also can act on sphingosylphosphphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP. Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation. Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. May have a role in induction of parturition. Possible involvement in cell proliferation and adipose tissue development. Tumor cell motility-stimulating factor.[1] [2] [3]

Publication Abstract from PubMed

Autotaxin (ATX, also known as Enpp2) is a secreted lysophospholipase D that hydrolyzes lysophosphatidylcholine to generate lysophosphatidic acid (LPA), a lipid mediator that activates G protein-coupled receptors to evoke various cellular responses. Here, we report the crystal structures of mouse ATX alone and in complex with LPAs with different acyl-chain lengths and saturations. These structures reveal that the multidomain architecture helps to maintain the structural rigidity of the lipid-binding pocket, which accommodates the respective LPA molecules in distinct conformations. They indicate that a loop region in the catalytic domain is a major determinant for the substrate specificity of the Enpp family enzymes. Furthermore, along with biochemical and biological data, these structures suggest that the produced LPAs are delivered from the active site to cognate G protein-coupled receptors through a hydrophobic channel.

Crystal structure of autotaxin and insight into GPCR activation by lipid mediators.,Nishimasu H, Okudaira S, Hama K, Mihara E, Dohmae N, Inoue A, Ishitani R, Takagi J, Aoki J, Nureki O Nat Struct Mol Biol. 2011 Feb;18(2):205-12. doi: 10.1038/nsmb.1998. Epub 2011 Jan, 16. PMID:21240269[4]

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

Loading citation details..
Citations
46 reviews cite this structure
Phospholipase D: enzymology, functionality, and chemical modulation.
Selvy et al. (2011)
45 more
92 other articles
No citations found

See Also

References

  1. ↑ Boucher J, Quilliot D, Praderes JP, Simon MF, Gres S, Guigne C, Prevot D, Ferry G, Boutin JA, Carpene C, Valet P, Saulnier-Blache JS. Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression. Diabetologia. 2005 Mar;48(3):569-77. Epub 2005 Feb 8. PMID:15700135 doi:10.1007/s00125-004-1660-8
  2. ↑ Pradere JP, Tarnus E, Gres S, Valet P, Saulnier-Blache JS. Secretion and lysophospholipase D activity of autotaxin by adipocytes are controlled by N-glycosylation and signal peptidase. Biochim Biophys Acta. 2007 Jan;1771(1):93-102. Epub 2006 Dec 6. PMID:17208043 doi:10.1016/j.bbalip.2006.11.010
  3. ↑ Nishimasu H, Okudaira S, Hama K, Mihara E, Dohmae N, Inoue A, Ishitani R, Takagi J, Aoki J, Nureki O. Crystal structure of autotaxin and insight into GPCR activation by lipid mediators. Nat Struct Mol Biol. 2011 Feb;18(2):205-12. doi: 10.1038/nsmb.1998. Epub 2011 Jan, 16. PMID:21240269 doi:10.1038/nsmb.1998
  4. ↑ Nishimasu H, Okudaira S, Hama K, Mihara E, Dohmae N, Inoue A, Ishitani R, Takagi J, Aoki J, Nureki O. Crystal structure of autotaxin and insight into GPCR activation by lipid mediators. Nat Struct Mol Biol. 2011 Feb;18(2):205-12. doi: 10.1038/nsmb.1998. Epub 2011 Jan, 16. PMID:21240269 doi:10.1038/nsmb.1998

Contents


PDB ID 3nkr

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/3nkr"
Personal tools