View source for 2cxs

[[Image:2cxs.gif|left|200px]]

<!--
The line below this paragraph, containing "STRUCTURE_2cxs", creates the "Structure Box" on the page.
You may change the PDB parameter (which sets the PDB file loaded into the applet) 
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
or leave the SCENE parameter empty for the default display.
-->
{{STRUCTURE_2cxs|  PDB=2cxs  |  SCENE=  }} 

'''Crystal structure of mouse AMF / F6P complex'''


==Overview==
Autocrine motility factor (AMF), a tumor-secreted cytokine, stimulates cell migration in vitro and metastasis in vivo. AMF is identical to the extracellular cytokines neuroleukin and maturation factor and, interestingly, to the intracellular enzyme phosphoglucose isomerase. The cytokine activity of AMF is inhibited by carbohydrate phosphate compounds as they compete for AMF binding with the carbohydrate moiety of the AMF receptor (AMFR), which is a glycosylated seven transmembrane helix protein. Here, we report the first comprehensive high-resolution crystal structure analyses of the inhibitor-free form and the eight types of inhibitor (phosphate, erythrose 4-phosphate (E4P), arabinose 5-phosphate (A5P), sorbitol 6-phosphate (S6P), 6-phosphogluconic acid (6PGA), fructose 6-phosphate (F6P), glucose 6-phosphate (G6P), or mannose 6-phosphate (M6P)) complexes of mouse AMF (mAMF). We assayed the inhibitory activities of these inhibitors against the cytokine activity of mAMF. The inhibitory activities of the six-carbon sugars (G6P, F6P, M6P, and 6PGA) were found to be significantly higher than those of the four or five-carbon sugars (E4P or A5P). The inhibitory activities clearly depend on the length of the inhibitor molecules. A structural comparison revealed that a water-mediated hydrogen bond between one end of the inhibitor and a rigid portion of the protein surface in the shorter-chain inhibitor (E4P) complex is replaced by a direct hydrogen bond in the longer-chain inhibitor (6PGA) complex. Thus, to obtain a new compound with higher inhibitory activities against AMF, water molecules at the inhibitor binding site of AMF should be replaced by a functional group of inhibitors in order to introduce direct interactions with the protein surface. The present structure-activity relationship studies will be valuable not only for designing more effective AMF inhibitors but also for studying general protein-inhibitor interactions.

==About this Structure==
2CXS is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CXS OCA]. 

==Reference==
Crystal structures of mouse autocrine motility factor in complex with carbohydrate phosphate inhibitors provide insight into structure-activity relationship of the inhibitors., Tanaka N, Haga A, Naba N, Shiraiwa K, Kusakabe Y, Hashimoto K, Funasaka T, Nagase H, Raz A, Nakamura KT, J Mol Biol. 2006 Feb 17;356(2):312-24. Epub 2005 Dec 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16375918 16375918]
[[Category: Glucose-6-phosphate isomerase]]
[[Category: Mus musculus]]
[[Category: Single protein]]
[[Category: Funasaka, T.]]
[[Category: Haga, A.]]
[[Category: Hashimoto, K.]]
[[Category: Kusakabe, Y.]]
[[Category: Naba, N.]]
[[Category: Nagase, H.]]
[[Category: Nakamura, K T.]]
[[Category: Raz, A.]]
[[Category: Shiraiwa, K.]]
[[Category: Tanaka, N.]]
[[Category: Isomerase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 23:18:43 2008''