2DOH

The X-ray crystallographic structure of the angiogenesis inhibitor, angiostatin, bound a to a peptide from the group A streptococcal surface protein PAM

Summary for 2DOH

• Entry DOI: 10.2210/pdb2doh/pdb
• Related: 2DOI
• Descriptor: Angiostatin, Plasminogen-binding group A streptococcal M-like protein PAM, 1,4-DIETHYLENE DIOXIDE, ... (4 entities in total)
• Functional Keywords: lysine-binding site, plasminogen, kringle domains, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted : P00747
• Total number of polymer chains: 2
• Total formula weight: 30464.72

Authors

Cnudde, S.E.,Prorok, M.,Castellino, F.J.,Geiger, J.H. (deposition date: 2006-04-29, release date: 2006-12-05, Last modification date: 2024-10-09)

Primary citation

Cnudde, S.E.,Prorok, M.,Castellino, F.J.,Geiger, J.H.
X-ray crystallographic structure of the angiogenesis inhibitor, angiostatin, bound to a peptide from the group A streptococcal surface protein PAM
Biochemistry, 45:11052-11060, 2006

PubMed Abstract: The crystal structure of the human Pg-derived angiogenesis inhibitor, angiostatin, complexed to VEK-30, a peptide from the group A streptococcal surface protein, PAM, was determined and refined to 2.3 A resolution. This is the first structure of angiostatin bound to a ligand and provides a model of the interaction between Pg and streptococcal-derived pathogenic proteins. VEK-30 contains a "through-space isostere" for C-terminal lysine, wherein Arg and Glu side chains, separated by one helical turn, bind within the bipolar angiostatin kringle 2 (K2) domain lysine-binding site. VEK-30 also makes several contacts with K2 residues that exist outside of the canonical LBS and are not conserved among the other Pg kringles, thus providing a molecular basis for the selectivity of VEK-30 for K2. The structure also shows that Pg kringle domains undergo significant structural rearrangement relative to one another and reveals dimerization between two molecules of angiostatin and VEK-30 related by crystallographic symmetry. This dimerization, which exists only in the crystal structure, is consistent with the parallel coiled-coil full-length PAM dimer expected from sequence similarities and homology modeling.

PubMed: 16964966
DOI: 10.1021/bi060914j

Experimental method

X-RAY DIFFRACTION (2.3 Å)