3hn7 | pdb_00003hn7
Crystal structure of a murein peptide ligase mpl (psyc_0032) from psychrobacter arcticus 273-4 at 1.65 A resolution
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBacterial cell walls contain peptidoglycan, an essential polymer made by enzymes in the Mur pathway. These proteins are specific to bacteria, which make them targets for drug discovery. MurC, MurD, MurE and MurF catalyze the synthesis of the peptidoglycan precursor UDP-N-acetylmuramoyl-L-alanyl-gamma-D-glutamyl-meso-diaminopimelyl-D-alany l-D-alanine by the sequential addition of amino acids onto UDP-N-acetylmuramic acid (UDP-MurNAc). MurC-F enzymes have been extensively studied by biochemistry and X-ray crystallography. In Gram-negative bacteria, approximately 30-60% of the bacterial cell wall is recycled during each generation. Part of this recycling process involves the murein peptide ligase (Mpl), which attaches the breakdown product, the tripeptide L-alanyl-gamma-D-glutamyl-meso-diaminopimelate, to UDP-MurNAc. We present the crystal structure at 1.65 A resolution of a full-length Mpl from the permafrost bacterium Psychrobacter arcticus 273-4 (PaMpl). Although the Mpl structure has similarities to Mur enzymes, it has unique sequence and structure features that are likely related to its role in cell wall recycling, a function that differentiates it from the MurC-F enzymes. We have analyzed the sequence-structure relationships that are unique to Mpl proteins and compared them to MurC-F ligases. We have also characterized the biochemical properties of this enzyme (optimal temperature, pH and magnesium binding profiles and kinetic parameters). Although the structure does not contain any bound substrates, we have identified approximately 30 residues that are likely to be important for recognition of the tripeptide and UDP-MurNAc substrates, as well as features that are unique to Psychrobacter Mpl proteins. These results provide the basis for future mutational studies for more extensive function characterization of the Mpl sequence-structure relationships. Structure and function of the first full-length murein Peptide ligase (mpl) cell wall recycling protein.,Das D, Herve M, Feuerhelm J, Farr CL, Chiu HJ, Elsliger MA, Knuth MW, Klock HE, Miller MD, Godzik A, Lesley SA, Deacon AM, Mengin-Lecreulx D, Wilson IA PLoS One. 2011 Mar 18;6(3):e17624. PMID:21445265[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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