1un5

File:1un5.gif

spinqualitylabelsall models 1un5, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

ARH-II, AN ANGIOGENIN/RNASE A CHIMERA

OverviewOverview

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.

About this StructureAbout this Structure

1UN5 is a Single protein structure of sequence from Homo sapiens with CIT as ligand. Active as Pancreatic ribonuclease, with EC number 3.1.27.5 Structure known Active Site: CIT. Full crystallographic information is available from OCA.

ReferenceReference

Crystallographic studies on structural features that determine the enzymatic specificity and potency of human angiogenin: Thr44, Thr80, and residues 38-41., Holloway DE, Chavali GB, Hares MC, Baker MD, Subbarao GV, Shapiro R, Acharya KR, Biochemistry. 2004 Feb 10;43(5):1230-41. PMID:14756559

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