1YF8

Crystal structure of Himalayan mistletoe RIP reveals the presence of a natural inhibitor and a new functionally active sugar-binding site

Summary for 1YF8

• Entry DOI: 10.2210/pdb1yf8/pdb
• Related PRD ID: PRD_900004
• Descriptor: Beta-galactoside-specific lectin 4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• Functional Keywords: himalayan mistletoe, ribosome inactivating protein, viscum album, natural inhibitor, sugar-binding site, hydrolase
• Biological source: Viscum album (European mistletoe); More
• Total number of polymer chains: 2
• Total formula weight: 57279.37

Authors

Mishra, V.,Bilgrami, S.,Sharma, R.S.,Kaur, P.,Yadav, S.,Betzel, C.,Babu, C.R.,Singh, T.P. (deposition date: 2004-12-31, release date: 2005-03-08, Last modification date: 2024-11-06)

Primary citation

Mishra, V.,Bilgrami, S.,Sharma, R.S.,Kaur, P.,Yadav, S.,Krauspenhaar, R.,Betzel, C.,Voelter, W.,Babu, C.R.,Singh, T.P.
Crystal structure of himalayan mistletoe ribosome-inactivating protein reveals the presence of a natural inhibitor and a new functionally active sugar-binding site.
J.Biol.Chem., 280:20712-20721, 2005

PubMed Abstract: Ribosome-inactivating proteins (RIPs) are toxins involved in plant defense. How the plant prevents autotoxicity is not yet fully understood. The present study is the first structural evidence of a naturally inhibited form of RIP from a plant. Himalayan mistletoe RIP (HmRIP) was purified from Viscum album leaves and crystallized with lactose. The structure was determined by the molecular replacement method and refined at 2.8-A resolution. The crystal structure revealed the presence of high quality non-protein electron density at the active site, into which a pteridine derivative (2-amino 4-isopropyl 6-carboxyl pteridine) was modeled. The carboxyl group of the ligand binds strongly with the key active site residue Arg(162), nullifies the positive charge required for catalysis, and thereby acts as a natural inhibitor. Lectin subunits of RIPs have two active sugar-binding sites present in 1alpha- and 2gamma-subdomains. A third functionally active site has been identified in the 1beta-subdomain of HmRIP. The 1beta-site is active despite the absence of conserved polar sugar-binding residues. Loss of these residues is compensated by the following: (i) the presence of an extended site where the penultimate sugar also interacts with the protein; (ii) the interactions of galactose with the protein main chain carbonyl and amide nitrogen atoms; (iii) the presence of a well defined pocket encircled by four walls; and (iv) a favorable stacking of the galactose ring with Tyr(66) besides the conserved Phe(75). The mode of sugar binding is also distinct at the 1alpha and 2gamma sugar-binding sites.

PubMed: 15774467
DOI: 10.1074/jbc.M500735200

Experimental method

X-RAY DIFFRACTION (2.8 Å)