1a4y
From Proteopedia
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==See Also== | ==See Also== | ||
*[[Ribonuclease inhibitor|Ribonuclease inhibitor]] | *[[Ribonuclease inhibitor|Ribonuclease inhibitor]] | ||
| - | *[[User:Jaime.Prilusky/Test/tree|User:Jaime.Prilusky/Test/tree]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 14:20, 15 February 2015
RIBONUCLEASE INHIBITOR-ANGIOGENIN COMPLEX
Structural highlights
Disease[ANGI_HUMAN] Defects in ANG are the cause of susceptibility to amyotrophic lateral sclerosis type 9 (ALS9) [MIM:611895]. ALS is a degenerative disorder of motor neurons in the cortex, brain stem and spinal cord. ALS is characterized by muscular weakness and atrophy.[1] [2] [3] [4] [5] [6] Function[RINI_HUMAN] Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and ANG. May play a role in redox homeostasis.[7] [8] [9] [ANGI_HUMAN] May function as a tRNA-specific ribonuclease that abolishes protein synthesis by specifically hydrolyzing cellular tRNAs. Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo.[10] [11] 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 PubMedHuman placental RNase inhibitor (hRI), a leucine-rich repeat protein, binds the blood vessel-inducing protein human angiogenin (Ang) with extraordinary affinity (Ki <1 fM). Here we report a 2.0 A resolution crystal structure for the hRI-Ang complex that, together with extensive mutagenesis data from earlier studies, reveals the molecular features of this tight interaction. The hRI-Ang binding interface is large and encompasses 26 residues from hRI and 24 from Ang, recruited from multiple domains of both proteins. However, a substantial fraction of the energetically important contacts involve only a single region of each: the C-terminal segment 434-460 of hRI and the ribonucleolytic active centre of Ang, most notably the catalytic residue Lys40. Although the overall docking of Ang resembles that observed for RNase A in the crystal structure of its complex with the porcine RNase inhibitor, the vast majority of the interactions in the two complexes are distinctive, indicating that the broad specificity of the inhibitor for pancreatic RNase superfamily proteins is based largely on its capacity to recognize features unique to each of them. The implications of these findings for the development of small, hRI-based inhibitors of Ang for therapeutic use are discussed. Molecular recognition of human angiogenin by placental ribonuclease inhibitor--an X-ray crystallographic study at 2.0 A resolution.,Papageorgiou AC, Shapiro R, Acharya KR EMBO J. 1997 Sep 1;16(17):5162-77. PMID:9311977[12] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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