1H53

Binding of Phosphate and Pyrophosphate ions at the active site of human Angiogenin as revealed by X-ray Crystallography

Summary for 1H53

• Entry DOI: 10.2210/pdb1h53/pdb
• Related: 1A4Y 1ANG 1AWZ 1B1E 1B1I 1B1J 1H52 1HBY 2ANG
• Descriptor: ANGIOGENIN, CITRIC ACID, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: angiogenin, ribonuclease, phosphate, pyrophosphate, hydrolase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 14368.02

Authors

Leonidas, D.D.,Chavali, G.B.,Jardine, A.M.,Li, S.,Shapiro, R.,Acharya, K.R. (deposition date: 2001-05-18, release date: 2001-08-09, Last modification date: 2023-12-13)

Primary citation

Leonidas, D.D.,Chavali, G.B.,Jardine, A.M.,Li, S.,Shapiro, R.,Acharya, K.R.
Binding of Phosphate and Pyrophosphate Ions at the Active Site of Human Angiogenin as Revealed by X-Ray Crystallography
Protein Sci., 10:1669-, 2001

PubMed Abstract: 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.

PubMed: 11468363
DOI: 10.1110/PS.13601

Experimental method

X-RAY DIFFRACTION (2 Å)