Alanine ligase

Tertiary treatment implemented Genes encoding D-alanine D-alanine ligases with a broad substrate specificity confer inducible resistance to the glycopeptides antibiotics, as vancomycin World Health Organization Wild-type... 

McDermott et al used rotational resonance, a then newly developed solid-state NMR method, for structural studies of an inhibited complex formed by reaction of D-alanine D-alanine ligase, ATP, and the aminoalkyl dipeptide analogue. The measured NMR coupling properties indicate that the two species are bridged in a P—O—P linkage, with a P—P through-space distance of 2.7 0.2 A. This work unambiguously demonstrated that the inactivation mechanism involves phosphorylation of enzyme-bound inhibitor by ATP to form a phos-phoryl-phosphinate adduct. ... 

ACYL-PHOSPHATE INTERMEDIATE d-ALANINE-d-ALANINE LIGASE... 

ALANINE AMINOTRANSFERASE y-GLUTAMYL TRANSPEPTIDASE l-SELENOCYSTEINE 13-LYASE d-ALANINE-d-ALANINE LIGASE ALANINE AMINOTRANSFERASE... 

ACETATE KINASE ACETYL-CoA CARBOXYLASE ACETYL-CoA SYNTHETASE N-ACETYLCLUCOSAMINE KINASE ACTIN ATPase ACTOMYOSIN ATPase N-ACYLMANNOSAMINE KINASE ADENINE NUCLEOTIDE TRANSLOCASE ADENOSINE KINASE ADENYLATE KINASE (MYOKINASE) ADENYLYLSULFATE KINASE d-ALANINE-d-ALANINE LIGASE... 

Bacterial cell wall synthesis inhibitor, d-ALANINE-d-ALANINE LIGASE BACTERIAL LEADER PEPTIDASE I Bacterial reorientation,... 

SLOW-BINDING INHIBITOR d-ALANINE-d-ALANINE LIGASE Slowest enzymic step in metabolic pathway, PACEMAKER ENZYME Slow partial exchange reactions,... 

OXYGEN, OXIDES 0X0 ANIONS Vancomycin-resistant enterococci, d-ALANYL-d-ALANINE LIGASE VAN DER WAALS FORCES VANT HOFF RELATIONSHIP COLLISION THEORY ARRHENIUS LAW TRANSITION-STATE THEORY TEMPERATURE DEPENDENCE VANT HOFF S LAWS VARIANCE... 

PK Chakravarty, WJ Greenleem, WH Parsons, AA Patchett, P Combs, A Roth, RD Busch, TN Mellin. (3-Amino-2-oxoalkyl)phosphponic acids and their analogs as novel inhibitors of D-alanine D-alanine ligase. J Med Chem 32 1886-1890, 1989. 

TDH Bugg, S Dutka-Malen, M Arthur, P Courvalin, CT Walsh. Identification of vancomycin resistance protein VanA as a D-alanine D-alanine ligase of altered substrate specificity. Biochemistry 30, 2017-2021, 1991. 

EJJ Lugtenberg, A van Schijndel-van Dam. Temperature-sensitive mutant of Escherichia coli K-12 with an impaired D-alanine D-alanine ligase. J Bacteriol 113 96— 104, 1973. 

E Daub, LE Zawadzke, D Botstein, CT Walsh. Isolation, cloning, and sequencing of the Salmonella typhimurium ddlA gene with purification and characterization of its product, D-alanine D-alanine ligase (ADP forming). Biochemistry 27 3701-3708, 1988. 

Chakravarty, P.K., Greenlee, W.J., Parsons, W.H., Patchett, A.A., Combs, P, Roth, A., Busch, R.D., and Mellin, T.N., (3-Amino-2-oxoalkyl)phosphonic acids and their analogues as novel inhibitors of D-alanine. c-Alanine ligase, J. Med. Chem., 32, 1886, 1989. 

Ozawa Y, Courvalin P, Gaiimand M (2000) Identification of enterococci at the species level by sequencing of the genes for D-alanine D-alanine ligases. Sys Appl Microbiol 23 230-237... 

Bouhss, A., Mengin-Lecreulx, D., Blanot, D., van Heijenoort, J., and Parquet, C. (1997) Invariant amino acids in the Mur peptide synthetases of bacterial peptidoglycan synthesis and their modification by site-directed mutagenesis in the UDP-MurNAc l-Alanine ligase from Escherichia coli. Biochemistry, 36, 11556-11563. 

Mol, C.D., Brooun, A., Dougan, D.R.M., Hilgers, T Tari, L.W., Wijnands, R.A., Knuth, M.W., McRee, D.E., and Swanson, R.V. (2003) Crystal structures of active fully assembled substrate- and product-bound complexes of UDP-N-acetyl-muramic add L-alanine-ligase (MurC) from Haemophilus influenza. J. Bacterial. 

Fig. 41.15. Sites of action of D-cycloserine 1, D-alanine racemase 2, D-alanine ligase.

D-Cycloserine 239 is a well-known antibiotic which inhibits alanine racemase and D-alanyl-D-alanine ligase [117]. The reactivity of the y-lactam carbonyl towards nucleophilic reagents is enhanced by the electronegative oxygen substituent. 

The bacterial cell wall is the first line of defense against environmental stress in gram-positive bacteria. Thus, selection schemes that change the cell wall structure can potentially make cells more resistant to environmental stress. D-cycloserine is an antibiotic that inhibits alanine racemase and D-alanine D-alanine ligase, both involved in cell wall biosynthesis. Mutants resistant to this antibiotic have been isolated in a number of gram-positive species and shown to have differences in surface properties (Clark Young, 1977 Reitz, Slade, Neuhaus, 1967). We have used D-cycloserine as a selective agent to directly select mutants in a variety of strains and found that the mutants obtained have properties useful in industrial fermentation processes. 

Carpenter CV, Neuhaus FC (1972) Enz3rmatic Synthesis of D-alanyl-D-alanine. Two Binding Modes for Product on D-alanine D-alanine Ligase (ADP). Biochemistry. 11 p. 2594-8. 

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