2bwk | pdb_00002bwk
MURINE ANGIOGENIN, SULPHATE COMPLEX
Structural highlights
Function[ANGI_MOUSE] Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Stimulates ribosomal RNA synthesis including that containing the initiation site sequences of 45S rRNA. Cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs) which inhibit protein synthesis and triggers the assembly of stress granules (SGs). Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo (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 PubMedAngiogenin is an unusual member of the pancreatic ribonuclease superfamily that induces blood-vessel formation and is a promising anticancer target. The three-dimensional structure of murine angiogenin (mAng) has been determined by X-ray crystallography. Two structures are presented: one is a complex with sulfate ions (1.5 Angstroms resolution) and the other a complex with phosphate ions (1.6 Angstroms resolution). Residues forming the putative B(1), P(1) and B(2) subsites occupy positions similar to their hAng counterparts and are likely to play similar roles. The anions occupy the P(1) subsite, sulfate binding conventionally and phosphate adopting two orientations, one of which is novel. The B(1) subsite is obstructed by Glu116 and Phe119, with the latter assuming a less invasive position than its hAng counterpart. Hydrophobic interactions between the C-terminal segment and the main body of the protein are more extensive than in hAng and may underly the lower enzymatic activity of the murine protein. Elsewhere, the structure of the H3-B2 loop supports the view that hAng Asn61 interacts directly with cell-surface molecules and does not merely stabilize adjacent regions of the hAng structure. mAng crystals appear to offer small-molecule inhibitors a clear route to the active site and may even withstand a reorientation of the C-terminal segment that provides access to the cryptic B(1) subsite. These features represent considerable advantages over crystalline hAng and bAng. Structure of murine angiogenin: features of the substrate- and cell-binding regions and prospects for inhibitor-binding studies.,Holloway DE, Chavali GB, Hares MC, Subramanian V, Acharya KR Acta Crystallogr D Biol Crystallogr. 2005 Dec;61(Pt 12):1568-78. Epub 2005, Nov 19. PMID:16301790[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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