1h53: Difference between revisions
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[[Image:1h53.jpg|left|200px]]<br /><applet load="1h53" size=" | [[Image:1h53.jpg|left|200px]]<br /><applet load="1h53" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1h53, resolution 2.00Å" /> | caption="1h53, resolution 2.00Å" /> | ||
'''BINDING OF PHOSPHATE AND PYROPHOSPHATE IONS AT THE ACTIVE SITE OF HUMAN ANGIOGENIN AS REVEALED BY X-RAY CRYSTALLOGRAPHY'''<br /> | '''BINDING OF PHOSPHATE AND PYROPHOSPHATE IONS AT THE ACTIVE SITE OF HUMAN ANGIOGENIN AS REVEALED BY X-RAY CRYSTALLOGRAPHY'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1H53 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PO4 and CIT as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=ACT:Ribonucleolytic Active Site'>ACT</scene> and <scene name='pdbsite=CIT:Cit Binding Site For Chain A'>CIT</scene>. Full crystallographic information is available from [http:// | 1H53 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=CIT:'>CIT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=ACT:Ribonucleolytic+Active+Site'>ACT</scene> and <scene name='pdbsite=CIT:Cit+Binding+Site+For+Chain+A'>CIT</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H53 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: ribonuclease]] | [[Category: ribonuclease]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:46:29 2008'' | ||
Revision as of 10:46, 3 February 2008
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BINDING OF PHOSPHATE AND PYROPHOSPHATE IONS AT THE ACTIVE SITE OF HUMAN ANGIOGENIN AS REVEALED BY X-RAY CRYSTALLOGRAPHY
OverviewOverview
Human angiogenin (Ang) is an unusual homolog of bovine pancreatic RNase A, that utilizes its ribonucleolytic activity to induce the formation of new, blood vessels. The pyrimidine-binding site of Ang was shown previously to, be blocked by glutamine 117, indicating that Ang must undergo a, conformational change to bind and cleave RNA. The mechanism and nature of, this change are not known, and no Ang-inhibitor complexes have been, characterized structurally thus far. Here, we report crystal structures, for the complexes of Ang with the inhibitors phosphate and pyrophosphate, and the structure of the complex of the superactive Ang variant Q117G with, phosphate, all at 2.0 A resolution. Phosphate binds to the catalytic site, of both Ang and Q117G in essentially the same manner observed in the RNase, A-phosphate complex, forming hydrogen bonds with the side chains of His, 13, His 114, and Gln 12, and the main chain of Leu 115; it makes an, additional interaction with the Lys 40 ammonium group in the Ang complex., One of the phosphate groups of pyrophosphate occupies a similar position., The other phosphate extends toward Gln 117, and lies within, hydrogen-bonding distance from the side-chain amide of this residue as, well as the imidazole group of His 13 and the main-chain oxygen of Leu, 115. The pyrimidine site remains obstructed in all three complex, structures, that is, binding to the catalytic center is not sufficient to, trigger the conformational change required for catalytic activity, even in, the absence of the Gln 117 side chain. The Ang-pyrophosphate complex, structure suggests how nucleoside pyrophosphate inhibitors might bind to, Ang; this information may be useful for the design of Ang antagonists as, potential anti-angiogenic drugs.
DiseaseDisease
Known diseases associated with this structure: Amyotrophic lateral sclerosis, susceptibility to OMIM:[105850]
About this StructureAbout this Structure
1H53 is a Single protein structure of sequence from Homo sapiens with and as ligands. Known structural/functional Sites: and . Full crystallographic information is available from OCA.
ReferenceReference
Binding of phosphate and pyrophosphate ions at the active site of human angiogenin as revealed by X-ray crystallography., Leonidas DD, Chavali GB, Jardine AM, Li S, Shapiro R, Acharya KR, Protein Sci. 2001 Aug;10(8):1669-76. PMID:11468363
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