2pi6 | pdb_00002pi6
Crystal structure of the sheep signalling glycoprotein (SPS-40) complex with 2-methyl-2-4-pentanediol at 1.65A resolution reveals specific binding characteristics of SPS-40
Structural highlights
FunctionCH3L1_SHEEP Carbohydrate-binding lectin with a preference for chitin. May play a role in defense against pathogens, or in tissue remodeling. May play an important role in the capacity of cells to respond to and cope with changes in their environment (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 40 kDa secretory signalling glycoprotein (SPS-40) is the first example with Trp78 in three functional orientations: (i) a resting state with a pinched conformation, (ii) a stacked conformation when bound to hexasaccharide and (iii) an obstructive conformation when inhibited by 2-methylpentane-2,4-diol (MPD). Trp78 is present in the core of the sugar-binding groove. The hexasaccharide N-acetylglucosamine (GlcNAc(6)) has been shown to bind to SPS-40. As a result of this, the conformation of Trp78 alters from the native pinched conformation (chi(1) = -65.5 degrees , chi(2,1) = -78.8 degrees , chi(2,2) = 97.5 degrees ) to the stacked conformation (chi(1) = -170.0 degrees , chi(2,1) = -114.3 degrees , chi(2,2) = 61.6 degrees ). Further binding experiments showed that saccharide binding does not occur in the presence of 20% MPD. The crystal structure determination of the complex of SPS-40 with MPD revealed the presence of two MPD molecules in the sugar-binding groove. The very tightly bound MPD molecules at subsites -2 and -1 induced an unexpected and a rarely observed conformation of Trp78 (chi(1) = 55.9 degrees , chi(2,1) = 90.2 degrees , chi(2,2) = -88.9 degrees ) which is termed an obstructive conformation. The binding of MPD molecules also twisted the side chains of Glu269 and Ile272 considerably. These residues are also part of the sugar-binding groove. The observed obstructive conformation of the side chain of Trp78 in the present structure is the exact opposite of the stacked conformation. This rarely observed conformation is stabilized by a number of hydrogen bonds between Trp78 and Asn79 through water molecules W49, W229, W269, W547 and W557. Tryptophan as a three-way switch in regulating the function of the secretory signalling glycoprotein (SPS-40) from mammary glands: structure of SPS-40 complexed with 2-methylpentane-2,4-diol at 1.6 A resolution.,Sharma P, Singh N, Sinha M, Sharma S, Perbandt M, Betzel C, Kaur P, Srinivasan A, Singh TP Acta Crystallogr D Biol Crystallogr. 2009 Apr;65(Pt 4):375-8. Epub 2009, Mar 19. PMID:19307719[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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