2doi
The X-ray crystallographic structure of the angiogenesis inhibitor, angiostatin, bound to a peptide from the group A streptococcus protein PAM
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OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Conjunctivitis, ligneous OMIM:[173350], Plasminogen Tochigi disease OMIM:[173350], Plasminogen deficiency, types I and II OMIM:[173350], Thrombophilia, dysplasminogenemic OMIM:[173350]
About this StructureAbout this Structure
2DOI is a Protein complex structure of sequences from Homo sapiens. Active as Plasmin, with EC number 3.4.21.7 Full crystallographic information is available from OCA.
ReferenceReference
X-ray crystallographic structure of the angiogenesis inhibitor, angiostatin, bound to a peptide from the group A streptococcal surface protein PAM., Cnudde SE, Prorok M, Castellino FJ, Geiger JH, Biochemistry. 2006 Sep 19;45(37):11052-60. PMID:16964966
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