3D6Q: The Rnase A- 5'-Deoxy-5'-N-Piperidinouridine Complex

Citation:
Abstract
Six 5'-deoxy-5'-morpholine, piperidine, and pyrrolidine of pyrimidine nucleosides have been synthesized and characterized. Their inhibitory action to ribonuclease A has been studied by biochemical analysis and X-ray crystallography. These compounds are moderate inhibitors of RNase A with mid-to-upper micromolar inhibition constants (K(i)). The high resolution X-ray crystal structures of the RNase A-inhibitor complexes have shown that all inhibitors bind at the enzyme catalytic cleft with the pyrimidine nucleobase at the B(1)R(2) subsites while the 5' group binds away from the main subsite P(1), where P-O(5') bond cleavage occurs, toward the solvent close to subsite P(0). Structure-activity relationship analysis has demonstrated that the compounds with the larger group in the 5' position are more potent. Comparative structural analysis of these RNase A complexes with other similar RNase A-ligand complexes provides a structural explanation of their potency and suggests ways to improve their efficiency and selectivity. These inhibitors can be the starting point for the development of compounds that can be used as pharmaceuticals against pathologies associated with RNase A homologues such as human angiogenin, which is implicated in tumor induced neovascularization.
PDB ID: 3D6QDownload
MMDB ID: 69536
PDB Deposition Date: 2008/5/20
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 1.6  Å
Source Organism:
Similar Structures:
Biological Unit for 3D6Q: monomeric; determined by author and by software (PISA)
Molecular Components in 3D6Q
Label Count Molecule
Protein (1 molecule)
1
Ribonuclease Pancreatic(Gene symbol: RNASE1)
Molecule annotation
Chemicals (3 molecules)
1
1
2
2
* Click molecule labels to explore molecular sequence information.

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