4B36

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

Summary for 4B36

• Entry DOI: 10.2210/pdb4b36/pdb
• Related: 1A4Y 1ANG 1AWZ 1B1E 1B1I 1B1J 1GV7 1H0D 1H52 1H53 1HBY 1K58 1K59 1K5A 1K5B 1UN3 1UN4 1UN5 2ANG 4AHD 4AHE 4AHF 4AHG 4AHH 4AHI 4AHJ 4AHK 4AHL 4AHM 4AHN 4AOH
• Descriptor: ANGIOGENIN, EOSINOPHIL CATIONIC-RELATED PROTEIN, CHLORIDE ION (3 entities in total)
• Functional Keywords: hydrolase, edn, ang, antiviral, angiogenesis, tumor, amyotrophic lateral sclerosis, parkinsons disease
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted, extracellular space, extracellular matrix, basement membrane: P03950
• Total number of polymer chains: 2
• Total formula weight: 29117.78

Authors

Thiyagarajan, N.,Acharya, K.R. (deposition date: 2012-07-20, release date: 2012-12-26, Last modification date: 2024-10-23)

Primary citation

Thiyagarajan, N.,Acharya, K.R.
Crystal Structure of Human Angiogenin with an Engineered Loop Exhibits Conformational Flexibility at the Functional Regions of the Molecule
FEBS Open Bio., 3:65-, 2012

PubMed Abstract: 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.

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

Experimental method

X-RAY DIFFRACTION (1.76 Å)