PDBsum entry 2zc5

Biosynthetic protein

PDB id: 2zc5

Contents

Protein chains

16 a.a.

384 a.a. *

Ligands

BMG ×2

Metals

_ZN ×8

Waters ×6

* Residue conservation analysis

PDB id:

2zc5

Name:

Biosynthetic protein

Title:

Penicillin-binding protein 1a (pbp 1a) acyl-enzyme complex (biapenem) from streptococcus pneumoniae

Structure:

Penicillin-binding protein 1a. Chain: a, c. Fragment: unp residues 47-70. Synonym: pbp-1a, exported protein 2. Engineered: yes. Other_details: transglycosylase domain. Penicillin-binding protein 1a. Chain: b, d. Fragment: unp residues 264-653.

Source:

Streptococcus pneumoniae. Gene: pbpa, exp2. Expressed in: escherichia coli. Gene: pbp1a.

Resolution:

3.00Å R-factor: 0.224 R-free: 0.276

Authors:

M.Yamada,T.Watanabe,Y.Takeuchi

Key ref:

M.Yamada et al. (2008). Crystal structures of biapenem and tebipenem complexed with penicillin-binding proteins 2X and 1A from Streptococcus pneumoniae. Antimicrob Agents Chemother, 52, 2053-2060. PubMed id: 18391040

Date:

02-Nov-07 Release date: 08-Apr-08

Protein chains

Q04707  (PBPA_STRPN) -  Penicillin-binding protein 1A from Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

Seq: 719 a.a.

Struc: 16 a.a.

Protein chains

Q04707  (PBPA_STRPN) -  Penicillin-binding protein 1A from Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

Seq: 719 a.a.

Struc: 384 a.a.*

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

Enzyme reactions

• Enzyme class 2: Chains A, B, C, D: E.C.2.4.99.28 - peptidoglycan glycosyltransferase.
• Reaction: [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)](n)- di-trans,octa-cis-undecaprenyl diphosphate + beta-D-GlcNAc-(1->4)- Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-di-trans,octa- cis-undecaprenyl diphosphate = [GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D- Glu-L-Lys-D-Ala-D-Ala)](n+1)-di-trans,octa-cis-undecaprenyl diphosphate + di-trans,octa-cis-undecaprenyl diphosphate + H⁺
• Enzyme class 3: Chains A, B, C, D: E.C.3.4.16.4 - serine-type D-Ala-D-Ala carboxypeptidase.
• Reaction: D-alanyl-D-alanine + H₂O = 2 D-alanine

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Antimicrob Agents Chemother 52:2053-2060 (2008)

PubMed id: 18391040

Crystal structures of biapenem and tebipenem complexed with penicillin-binding proteins 2X and 1A from Streptococcus pneumoniae.

M.Yamada, T.Watanabe, N.Baba, Y.Takeuchi, F.Ohsawa, S.Gomi.

ABSTRACT

Biapenem is a parenteral carbapenem antibiotic that exhibits wide-ranging antibacterial activity, remarkable chemical stability, and extensive stability against human renal dehydropeptidase-I. Tebipenem is the active form of tebipenem pivoxil, a novel oral carbapenem antibiotic that has a high level of bioavailability in humans, in addition to the above-mentioned features. beta-lactam antibiotics, including carbapenems, target penicillin-binding proteins (PBPs), which are membrane-associated enzymes that play essential roles in peptidoglycan biosynthesis. To envisage the binding of carbapenems to PBPs, we determined the crystal structures of the trypsin-digested forms of both PBP 2X and PBP 1A from Streptococcus pneumoniae strain R6, each complexed with biapenem or tebipenem. The structures of the complexes revealed that the carbapenem C-2 side chains form hydrophobic interactions with Trp374 and Thr526 of PBP 2X and with Trp411 and Thr543 of PBP 1A. The Trp and Thr residues are conserved in PBP 2B. These results suggest that interactions between the C-2 side chains of carbapenems and the conserved Trp and Thr residues in PBPs play important roles in the binding of carbapenems to PBPs.