PDBsum entry: 2doi

Hydrolase

PDB id: 2doi

Contents

Protein chains

168 a.a. *

24 a.a. *

24 a.a. *

* Residue conservation analysis

PDB id:

2doi

Name:

Hydrolase

Title:

The x-ray crystallographic structure of the angiogenesis inh angiostatin, bound to a peptide from the group a streptococ protein pam

Structure:

Angiostatin. Chain: x, a. Fragment: kringle 1,kringle 2 and kringle 3. Engineered: yes. Mutation: yes. Plasminogen-binding group a streptococcal m-like pam. Chain: c, b. 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 the streptococcus protein pam

Biol. unit:

Dimer (from PQS)

Resolution:

3.10Å R-factor: 0.202 R-free: 0.296

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

Date:

29-Apr-06 Release date: 05-Dec-06

Protein chains

P00747  (PLMN_HUMAN) -  Plasminogen

Seq: 810 a.a.

Struc: 168 a.a.*

Protein chain

P49054  (PAM_STRPY) -  Plasminogen-binding group A steptococcal M-like protein PAM (Fragment)

Seq: 388 a.a.

Struc: 24 a.a.

Protein chain

P49054  (PAM_STRPY) -  Plasminogen-binding group A steptococcal M-like protein PAM (Fragment)

Seq: 388 a.a.

Struc: 24 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains X, A: E.C.3.4.21.7 - Plasmin.
• Reaction: Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa; higher selectivity than trypsin. Converts fibrin into soluble products.

 Gene Ontology (GO) functional annotation 

• 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.

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.