1A4Y

RIBONUCLEASE INHIBITOR-ANGIOGENIN COMPLEX

Summary for 1A4Y

• Entry DOI: 10.2210/pdb1a4y/pdb
• Descriptor: RIBONUCLEASE INHIBITOR, ANGIOGENIN (3 entities in total)
• Functional Keywords: complex (inhibitor-nuclease), complex (ri-ang), hydrolase molecular recognition, epitope mapping, leucine-rich repeats, complex (inhibitor-nuclease) complex, complex (inhibitor/nuclease)
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P13489; Cytoplasmic vesicle, secretory vesicle lumen : P03950
• Total number of polymer chains: 4
• Total formula weight: 128112.38

Authors

Papageorgiou, A.C.,Acharya, K.R. (deposition date: 1998-02-08, release date: 1998-10-14, Last modification date: 2024-10-16)

Primary citation

Papageorgiou, A.C.,Shapiro, R.,Acharya, K.R.
Molecular recognition of human angiogenin by placental ribonuclease inhibitor--an X-ray crystallographic study at 2.0 A resolution.
EMBO J., 16:5162-5177, 1997

PubMed Abstract: Human 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.

PubMed: 9311977
DOI: 10.1093/emboj/16.17.5162

Experimental method

X-RAY DIFFRACTION (2 Å)