PDBsum entry 2eav

Sugar binding protein

PDB id: 2eav

Contents

Protein chain

164 a.a. *

Metals

_NI ×6

Waters ×139

* Residue conservation analysis

PDB id:

2eav

Name:

Sugar binding protein

Title:

Crystal structure of thE C-terminal peptidoglycan-binding domain of human peptidoglycan recognition protein ibeta

Structure:

Peptidoglycan recognition protein-i-beta. Chain: a, b. Fragment: peptidoglycan-binding domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: pgrpib. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.20Å R-factor: 0.229 R-free: 0.285

Authors:

S.Cho,R.A.Mariuzza

Key ref:

S.Cho et al. (2007). Structural insights into the bactericidal mechanism of human peptidoglycan recognition proteins. Proc Natl Acad Sci U S A, 104, 8761-8766. PubMed id: 17502600 DOI: 10.1073/pnas.0701453104

Date:

03-Feb-07 Release date: 18-Sep-07

Protein chains

Q96LB8  (PGRP4_HUMAN) -  Peptidoglycan recognition protein 4 from Homo sapiens

Seq: 373 a.a.

Struc: 164 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1073/pnas.0701453104

Proc Natl Acad Sci U S A 104:8761-8766 (2007)

PubMed id: 17502600

Structural insights into the bactericidal mechanism of human peptidoglycan recognition proteins.

S.Cho, Q.Wang, C.P.Swaminathan, D.Hesek, M.Lee, G.J.Boons, S.Mobashery, R.A.Mariuzza.

ABSTRACT

Peptidoglycan recognition proteins (PGRPs) are highly conserved pattern-recognition molecules of the innate immune system that bind bacterial peptidoglycans (PGNs), which are polymers of alternating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) cross-linked by short peptide stems. Human PRGPs are bactericidal against pathogenic and nonpathogenic Gram-positive bacteria, but not normal flora bacteria. Like certain glycopeptide antibiotics (e.g., vancomycin), PGRPs kill bacteria by directly interacting with their cell wall PGN, thereby interfering with PGN maturation. To better understand the bactericidal mechanism of PGRPs, we determined the crystal structure of the C-terminal PGN-binding domain of human PGRP-Ibeta in complex with NAG-NAM-l-Ala-gamma-d-Glu-l-Lys-d-Ala-d-Ala, a synthetic glycopeptide comprising a complete PGN repeat. This structure, in conjunction with the previously reported NMR structure of a dimeric PGN fragment, permitted identification of major conformational differences between free and PGRP-bound PGN with respect to the relative orientation of saccharide and peptide moieties. These differences provided structural insights into the bactericidal mechanism of human PGRPs. On the basis of molecular modeling, we propose that these proteins disrupt cell wall maturation not only by sterically encumbering access of biosynthetic enzymes to the nascent PGN chains, but also by locking PGN into a conformation that prevents formation of cross-links between peptide stems in the growing cell wall.

Selected figure(s)

Figure 1.
Fig. 1. Structure of PGN and PGN derivatives. (A) Schematic representation of Lys-type PGNs. Lys-type PGN peptides are usually cross-linked through a peptide bridge composed of one to five glycines. The fragment shown in red corresponds to GMPP. (B) Chemical structure of GMPP. (C) GMPP[2]. (D) MPP (R^1, H) and MPP-Dap (R^1, COOH).

Figure 3.
Fig. 3. Structural comparison between PGRP-bound PGN analogs in crystal structures and unbound GMPP[2] in solution. (A) Conformational comparison of GMPP, MPP, TCT, and GMPP[2]. GMPP, MPP, and TCT are from crystal structures of complexes with human PGRP-I C, human PGRP-I C (16), and Drosophila PGRP-LE (27), respectively; GMPP[2] is from the unliganded NMR structure (17). The structures are superposed through the pyranose ring of NAM (for MPP, GMPP, and GMPP[2]) or NAM(1,6-anhydro) (for TCT). (B) Superposition of unbound GMPP[2] onto GMPP in the PGRP-I C–GMPP complex. GMPP and GMPP[2] are shown in ball-and-stick representations, with carbon atoms in yellow and green, respectively, nitrogen atoms in blue, and oxygen atoms in red. Of the two GMPP units in GMPP[2], the first unit, comprising the NAG[1]-NAM[1] disaccharide, is superposed onto GMPP in the complex. The peptide stem of GMPP[2] attached to NAM[1] is buried within PGRP-I C and is shown in pale green. (C) Alternative superposition of unliganded GMPP[2] onto GMPP bound to PGRP-I C. In this case, the second GMPP unit of GMPP[2], containing NAG[2]-NAM[2], is superposed onto GMPP in the PGRP-I C–GMPP structure. The peptide stem of GMPP[2] attached to NAM[2], shown in pale green, is buried inside PGRP-I C. (D) Modeled PGRP-I C–GMPP[2] structure.

Figures were selected by an automated process.