2doh
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The crystal structure of the human Pg-derived angiogenesis inhibitor, angiostatin, complexed to VEK-30, a peptide from the group A streptococcal | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Plasmin]] | [[Category: Plasmin]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Castellino, F | + | [[Category: Castellino, F J.]] |
| - | [[Category: Cnudde, S | + | [[Category: Cnudde, S E.]] |
| - | [[Category: Geiger, J | + | [[Category: Geiger, J H.]] |
[[Category: Prorok, M.]] | [[Category: Prorok, M.]] | ||
[[Category: DIO]] | [[Category: DIO]] | ||
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[[Category: plasminogen]] | [[Category: plasminogen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:00:58 2008'' |
Revision as of 15:00, 21 February 2008
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The X-ray crystallographic structure of the angiogenesis inhibitor, angiostatin, bound a to a peptide from the group A streptococcal surface protein PAM
Contents |
Overview
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.
Disease
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 Structure
2DOH is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Plasmin, with EC number 3.4.21.7 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 17:00:58 2008
