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1ehi
From Proteopedia
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|PDB= 1ehi |SIZE=350|CAPTION= <scene name='initialview01'>1ehi</scene>, resolution 2.38Å | |PDB= 1ehi |SIZE=350|CAPTION= <scene name='initialview01'>1ehi</scene>, resolution 2.38Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ADP:ADENOSINE-5 | + | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene> and <scene name='pdbligand=PHY:1(S)-AMINOETHYL-(2-CARBOXYPROPYL)PHOSPHORYL-PHOSPHINIC ACID'>PHY</scene> |
|ACTIVITY= [http://en.wikipedia.org/wiki/D-alanine--D-alanine_ligase D-alanine--D-alanine ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.4 6.3.2.4] | |ACTIVITY= [http://en.wikipedia.org/wiki/D-alanine--D-alanine_ligase D-alanine--D-alanine ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.3.2.4 6.3.2.4] | ||
|GENE= | |GENE= | ||
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[[Category: atp-binding. grasp motif for atp.]] | [[Category: atp-binding. grasp motif for atp.]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 11:39:31 2008'' |
Revision as of 09:39, 23 March 2008
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| , resolution 2.38Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Activity: | D-alanine--D-alanine ligase, with EC number 6.3.2.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
D-ALANINE:D-LACTATE LIGASE (LMDDL2) OF VANCOMYCIN-RESISTANT LEUCONOSTOC MESENTEROIDES
Overview
BACKGROUND: The bacterial cell wall and the enzymes that synthesize it are targets of glycopeptide antibiotics (vancomycins and teicoplanins) and beta-lactams (penicillins and cephalosporins). Biosynthesis of cell wall peptidoglycan requires a crosslinking of peptidyl moieties on adjacent glycan strands. The D-alanine-D-alanine transpeptidase, which catalyzes this crosslinking, is the target of beta-lactam antibiotics. Glycopeptides, in contrast, do not inhibit an enzyme, but bind directly to D-alanine-D-alanine and prevent subsequent crosslinking by the transpeptidase. Clinical resistance to vancomycin in enterococcal pathogens has been traced to altered ligases producing D-alanine-D-lactate rather than D-alanine-D-alanine. RESULTS: The structure of a D-alanine-D-lactate ligase has been determined by multiple anomalous dispersion (MAD) phasing to 2.4 A resolution. Co-crystallization of the Leuconostoc mesenteroides LmDdl2 ligase with ATP and a di-D-methylphosphinate produced ADP and a phosphinophosphate analog of the reaction intermediate of cell wall peptidoglycan biosynthesis. Comparison of this D-alanine-D-lactate ligase with the known structure of DdlB D-alanine-D-alanine ligase, a wild-type enzyme that does not provide vancomycin resistance, reveals alterations in the size and hydrophobicity of the site for D-lactate binding (subsite 2). A decrease was noted in the ability of the ligase to hydrogen bond a substrate molecule entering subsite 2. CONCLUSIONS: Structural differences at subsite 2 of the D-alanine-D-lactate ligase help explain a substrate specificity shift (D-alanine to D-lactate) leading to remodeled cell wall peptidoglycan and vancomycin resistance in Gram-positive pathogens.
About this Structure
1EHI is a Single protein structure of sequence from Leuconostoc mesenteroides. Full crystallographic information is available from OCA.
Reference
Enzymes of vancomycin resistance: the structure of D-alanine-D-lactate ligase of naturally resistant Leuconostoc mesenteroides., Kuzin AP, Sun T, Jorczak-Baillass J, Healy VL, Walsh CT, Knox JR, Structure. 2000 May 15;8(5):463-70. PMID:10801495
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