ISDA: 4B36

Deposition Date 2012-07-20

Release Date 2012-12-26

Last Version Date 2024-10-23

Entry Detail

PDB ID:

4B36

Keywords:

HYDROLASE

Title:

Crystal Structure of Human Angiogenin with an Engineered Loop Exhibits Conformational Flexibility at the Functional Regions of the Molecule

Biological Source:

Source Organism(s):

HOMO SAPIENS (Taxon ID: 9606)

Expression System(s):

Escherichia coli

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

1.76 Å

R-Value Free:

0.28

R-Value Work:

0.23

R-Value Observed:

0.23

Space Group:

P 21 21 21

Download Validation Report

Macromolecular Entities

Structures with similar UniProt ID

Structural Superimposition Protein Blast

Polymer Type:polypeptide(L)
Molecule:ANGIOGENIN, EOSINOPHIL CATION
Gene (Uniprot):ANG
Chain IDs:A, B
Chain Length:126
Number of Molecules:2
Biological Source:HOMO SAPIENS

UniProt ID:P03950 Pfam ID:PF00074 EC:3.1.27.-

Ligand Molecules

Primary Citation

Crystal Structure of Human Angiogenin with an Engineered Loop Exhibits Conformational Flexibility at the Functional Regions of the Molecule

Thiyagarajan, N, Acharya, K.R.Show

FEBS Open Bio. 3 65 ? (2012)

PMID: 23772376 DOI: 10.1016/J.FOB.2012.12.003

Abstact

Human angiogenin (ANG) is an angiogenic molecule and a ribonucleolytic enzyme with significant amino acid sequence identity to pancreatic RNase A, plays a critical role in the establishment and growth of tumours. An association between ANG and cancer has been observed in more than 25 clinical studies to date. In addition, ANG has now been shown to be implicated in Amyotrophic Lateral Sclerosis (ALS) and Parkinson's Disease (PD). Structural and biochemical studies so far have showed several distinguishing features of ANG molecule compared to RNase A and provided details of the putative cell binding site, active site, nuclear translocation sequence and the roles of residues in binding and cleaving RNA. A key finding elucidated from the structural study on ANG is the presence of a 'blocked' C-terminus (part of the active site apparatus) compared with RNase A. Here we report the crystal structure of ANG with an 'engineered-loop' from eosinophil derived neurotoxin (a homologue of ANG) which has resulted with local perturbations (conformational flexibility) at the cell binding site and at the C-terminus of the molecule. This experimental observation will now provide a new avenue to design compounds (potent inhibitors) through a structure guided drug design route.

Legend

Protein

Chemical

Disease

Primary Citation of related structures

Abstact

Feedback Form