1a4y: Difference between revisions
New page: left|200px<br /> <applet load="1a4y" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a4y, resolution 2.0Å" /> '''RIBONUCLEASE INHIBIT... |
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[[Image:1a4y.gif|left|200px]]<br /> | [[Image:1a4y.gif|left|200px]]<br /><applet load="1a4y" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1a4y, resolution 2.0Å" /> | caption="1a4y, resolution 2.0Å" /> | ||
'''RIBONUCLEASE INHIBITOR-ANGIOGENIN COMPLEX'''<br /> | '''RIBONUCLEASE INHIBITOR-ANGIOGENIN COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
Human placental RNase inhibitor (hRI), a leucine-rich repeat protein, binds the blood vessel-inducing protein human angiogenin (Ang) with | 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. | ||
==Disease== | ==Disease== | ||
Known diseases associated with this structure: Amyotrophic lateral sclerosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=105850 105850]], Creutzfeldt-Jakob disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Gerstmann-Straussler disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Huntington disease-like 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Insomnia, fatal familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Prion disease with protracted course OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]] | Known diseases associated with this structure: Aicardi-Goutieres syndrome 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606034 606034]], Amyotrophic lateral sclerosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=105850 105850]], Creutzfeldt-Jakob disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Gerstmann-Straussler disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Huntington disease-like 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Insomnia, fatal familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]], Prion disease with protracted course OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176640 176640]] | ||
==About this Structure== | ==About this Structure== | ||
1A4Y is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 1A4Y is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A4Y OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Acharya, K | [[Category: Acharya, K R.]] | ||
[[Category: Papageorgiou, A | [[Category: Papageorgiou, A C.]] | ||
[[Category: complex (inhibitor/nuclease)]] | [[Category: complex (inhibitor/nuclease)]] | ||
[[Category: complex (ri-ang)]] | [[Category: complex (ri-ang)]] | ||
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[[Category: leucine-rich repeats]] | [[Category: leucine-rich repeats]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:40:53 2008'' | ||
Revision as of 12:40, 21 February 2008
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RIBONUCLEASE INHIBITOR-ANGIOGENIN COMPLEX
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Aicardi-Goutieres syndrome 4 OMIM:[606034], Amyotrophic lateral sclerosis, susceptibility to OMIM:[105850], Creutzfeldt-Jakob disease OMIM:[176640], Gerstmann-Straussler disease OMIM:[176640], Huntington disease-like 1 OMIM:[176640], Insomnia, fatal familial OMIM:[176640], Prion disease with protracted course OMIM:[176640]
About this StructureAbout this Structure
1A4Y is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
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