PDBsum entry 2doh

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Hydrolase PDB id
Protein chains
165 a.a. *
24 a.a. *
Waters ×313
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: The x-ray crystallographic structure of the angiogenesis inh angiostatin, bound a to a peptide from the group a streptoc surface protein pam
Structure: Angiostatin. Chain: x. Fragment: kringle 1,kringle 2 and kringle 3. Engineered: yes. Mutation: yes. Plasminogen-binding group a streptococcal m-like pam. Chain: c. Fragment: vek-30.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: plg. Expressed in: pichia pastoris. Expression_system_taxid: 4922. Synthetic: yes. Other_details: vek-30 is an internal peptide within pam
Biol. unit: Dimer (from PQS)
2.30Å     R-factor:   0.210     R-free:   0.260
Authors: S.E.Cnudde,M.Prorok,F.J.Castellino,J.H.Geiger
Key ref:
S.E.Cnudde et al. (2006). 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. PubMed id: 16964966 DOI: 10.1021/bi060914j
29-Apr-06     Release date:   05-Dec-06    
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Protein chain
Pfam   ArchSchema ?
P00747  (PLMN_HUMAN) -  Plasminogen
810 a.a.
165 a.a.
Protein chain
Pfam   ArchSchema ?
P49054  (PAM_STRPY) -  Plasminogen-binding group A streptococcal M-like protein PAM (Fragment)
388 a.a.
24 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chain X: E.C.  - Plasmin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa; higher selectivity than trypsin. Converts fibrin into soluble products.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     blood coagulation   2 terms 
  Biochemical function     calcium ion binding     2 terms  


DOI no: 10.1021/bi060914j Biochemistry 45:11052-11060 (2006)
PubMed id: 16964966  
X-ray crystallographic structure of the angiogenesis inhibitor, angiostatin, bound to a peptide from the group A streptococcal surface protein PAM.
S.E.Cnudde, M.Prorok, F.J.Castellino, J.H.Geiger.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19800007 M.Wang, J.Zajicek, J.H.Geiger, M.Prorok, and F.J.Castellino (2010).
Solution structure of the complex of VEK-30 and plasminogen kringle 2.
  J Struct Biol, 169, 349-359.
PDB code: 2kj4
19473980 A.C.Tharp, M.Laha, P.Panizzi, M.W.Thompson, P.Fuentes-Prior, and P.E.Bock (2009).
Plasminogen Substrate Recognition by the Streptokinase-Plasminogen Catalytic Complex Is Facilitated by Arg253, Lys256, and Lys257 in the Streptokinase {beta}-Domain and Kringle 5 of the Substrate.
  J Biol Chem, 284, 19511-19521.  
18039665 Q.Fu, M.Figuera-Losada, V.A.Ploplis, S.Cnudde, J.H.Geiger, M.Prorok, and F.J.Castellino (2008).
The lack of binding of VEK-30, an internal peptide from the group A streptococcal M-like protein, PAM, to murine plasminogen is due to two amino acid replacements in the plasminogen kringle-2 domain.
  J Biol Chem, 283, 1580-1587.  
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