PDBsum entry 2pms

Metal transport, hydrolase

PDB id: 2pms

Contents

Protein chains

331 a.a. *

109 a.a. *

Ligands

NAG ×2

CO3 ×2

SO4 ×6

Metals

_ZN ×2

_FE ×2

Waters ×24

* Residue conservation analysis

PDB id:

2pms

Name:

Metal transport, hydrolase

Title:

Crystal structure of the complex of human lactoferrin n-lobe and lactoferrin-binding domain of pneumococcal surface protein a

Structure:

Lactotransferrin. Chain: a, b. Fragment: n-terminal lobe. Synonym: lactoferrin, talalactoferrin alfa. Engineered: yes. Pneumococcal surface protein a (pspa). Chain: c, d. Fragment: lactoferrin-binding domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ltf, lf. Expressed in: insect cells. Streptococcus pneumoniae. Organism_taxid: 1313. Strain: rx1. Gene: pspa.

Resolution:

2.91Å R-factor: 0.205 R-free: 0.249

Authors:

D.Chattopadhyay,O.Senkovich,W.J.Cook

Key ref:

O.Senkovich et al. (2007). Structure of a Complex of Human Lactoferrin N-lobe with Pneumococcal Surface Protein A Provides Insight into Microbial Defense Mechanism. J Mol Biol, 370, 701-713. PubMed id: 17543335 DOI: 10.1016/j.jmb.2007.04.075

Date:

23-Apr-07 Release date: 19-Jun-07

Protein chains

P02788  (TRFL_HUMAN) -  Lactotransferrin from Homo sapiens

Seq: 710 a.a.

Struc: 331 a.a.*

Protein chains

Q54972  (Q54972_STREE) -  Pneumococcal surface protein A from Streptococcus pneumoniae

Seq: 619 a.a.

Struc: 109 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.4.21.- - ?????

DOI no: 10.1016/j.jmb.2007.04.075

J Mol Biol 370:701-713 (2007)

PubMed id: 17543335

Structure of a Complex of Human Lactoferrin N-lobe with Pneumococcal Surface Protein A Provides Insight into Microbial Defense Mechanism.

O.Senkovich, W.J.Cook, S.Mirza, S.K.Hollingshead, I.I.Protasevich, D.E.Briles, D.Chattopadhyay.

ABSTRACT

Human lactoferrin, a component of the innate immune system, kills a wide variety of microorganisms including the Gram positive bacteria Streptococcus pneumoniae. Pneumococcal surface protein A (PspA) efficiently inhibits this bactericidal action. The crystal structure of a complex of the lactoferrin-binding domain of PspA with the N-lobe of human lactoferrin reveals direct and specific interactions between the negatively charged surface of PspA helices and the highly cationic lactoferricin moiety of lactoferrin. Binding of PspA blocks surface accessibility of this bactericidal peptide preventing it from penetrating the bacterial membrane. Results of site-directed mutagenesis, in vitro protein binding assays and isothermal titration calorimetry measurements corroborate that the specific electrostatic interactions observed in the crystal structure represent major associations between PspA and lactoferrin. The structure provides a snapshot of the protective mechanism utilized by pathogens against the host's first line of defense. PspA represents a major virulence factor and a promising vaccine candidate. Insights from the structure of the complex have implications for designing therapeutic strategies for treatment and prevention of pneumococcal diseases that remain a major public health problem worldwide.

Selected figure(s)

Figure 1.
Figure 1. Structure of the PspA[2]:NLF complex. (a) Asymmetric unit content. LF N-lobes are shown in green (Lfcn peptide is colored blue), PspA[2] molecules in red. One Fe ion (orange) is bound to each NLF. The coordinating carbonate ligand is shown in sticks. One Zn ion (cyan) is bound at the N-terminal end of each PspA[2] molecule. The N-acetylglucosamine molecule is labeled NAG. (b) PspA[2] structure. Residue numbering for PspA[2] helices are shown.

Figure 7.
Figure 7. (a) Superposition of the NMR structure of intact LfcnH peptide (yellow) on the lactoferricin domain (residues 3–49) of the NLF (green) from the PspA[2]:NLF complex. The conformation of the first helix of the Lfcn domain is very similar in both structures although the β-sheet is unfolded in the LfcnH peptide. (b) Residues in the first helix of NLF (green) that interact with various residues of PspA[2] (salmon) are shown in stick model. This helix of NLF provides many contacts with PspA. The corresponding section of LfcnH peptide is shown in yellow.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 370, 701-713) copyright 2007.

Figures were selected by an automated process.