Summary for 1UN4
| Entry DOI | 10.2210/pdb1un4/pdb |
| Related | 1A4Y 1ANG 1AWZ 1B1E 1B1I 1B1J 1GV7 1H0D 1H52 1H53 1HBY 1K58 1K59 1K5A 1K5B 1UN3 1UN5 2ANG |
| Descriptor | ANGIOGENIN, CITRIC ACID (3 entities in total) |
| Functional Keywords | ribonuclease, hydrolase, nuclease, endonuclease, angiogenesis, pyrrolidone carboxylic acid |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 14314.10 |
| Authors | Holloway, D.E.,Chavali, G.B.,Acharya, K.R. (deposition date: 2003-09-04, release date: 2004-02-06, Last modification date: 2024-11-13) |
| Primary citation | Holloway, D.E.,Chavali, G.B.,Hares, M.C.,Baker, M.D.,Subbarao, G.V.,Shapiro, R.,Acharya, K.R. Crystallographic Studies on Structural Features that Determine the Enzymatic Specificity and Potency of Human Angiogenin: Thr44, Thr80 and Residues 38-41 Biochemistry, 43:1230-, 2004 Cited by PubMed Abstract: Human angiogenin (Ang) is a potent inducer of blood vessel formation and is a member of the pancreatic ribonuclease superfamily. Its enzymatic activity is unusually weak and biased toward cleavage after cytidine nucleotides. As part of an ongoing investigation into the structural basis of Ang's characteristic activity, we have determined the crystal structures of three Ang variants having novel activity. (i) The structure of T44D-Ang indicates that Asp44 can participate directly in pyrimidine binding and that the intrinsic hydrogen-bonding capability of this residue largely governs the pyrimidine specificity of this variant. Unexpectedly, the mutation also causes the most extensive disruption of the C-terminus seen in any Ang variant thus far. This allows the side chain of Arg101 to penetrate the B(1) site, raising the possibility that it participates in substrate binding as occurs in ribonuclease 4. (ii) The structure of T80A-Ang supports the view that Thr80 plays little role in maintaining the obstructive conformation of the C-terminus and that its participation in a hydrogen bond with Thr44 selectively weakens the interaction between Thr44 and N3 of cytosine. (iii) ARH-II is an angiogenin/RNase A chimera in which residues 38-41 of Ang are replaced with the corresponding residues (38-42) of RNase A. Its structure suggests that the guest segment influences catalysis by subtle means, possibly by reducing the pK(a) of the catalytic lysine. The loss of angiogenic activity is not attributable to disruption of known cell-binding or nuclear translocation sites but may be a consequence of the chimera's enhanced ribonucleolytic activity. PubMed: 14756559DOI: 10.1021/BI035654+ PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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