Vancomycin Resistance: Structure of D-Alanine:D-Alanine Ligase at 2.3 Å Resolution

Chang, Fan; Moews, Paul C.; Walsh, Christopher T.; Knox, James R.

doi:10.1126/science.7939684

Cited by 255 publications

(346 citation statements)

References 28 publications

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“…The a-phosphate group forms equivalent hydrogen bonds with the side chains of Lys72 (cAPK), Lys144 (DDligase), and Lys9 (RNR RI). These lysine residues are conserved throughout each of these three families (Hanks et al, 1988;Fan et al, 1994;Stapleton et al, 1996;Eriksson et al, 1997;Galperin & Koonin, 1997;Dideberg & Bertrand, 1998;Esser et al, 1998).…”

Section: Resultsmentioning

confidence: 99%

“…These last two fold classes are particularly interesting. Although the folds are different, two of their typical members, CAMP-dependent protein kinase (cAPK) from the one family (Bossemeyer et al, 1993) and D-Ala:D-Ala ligase (m-ligase) from the other family (Fan et al, 1994(Fan et al, , 1997, have over 100 structurally-equivalent residues from ten segments that form two identical supersecondary structures between which the cofactor ATP is bound in a similar way (Denessiouk et al, 1998).…”

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confidence: 99%

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Enzyme‐mononucleotide interactions: Three different folds share common structural elements for atp recognition

1998

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Three ATP-dependent enzymes with different folds, CAMP-dependent protein kinase, D-Ala:o-Ala ligase and the a-subunit of the a2P2 ribonucleotide reductase, have a similar organization of their ATP-binding sites. The most meaningful similarity was found over 23 structurally equivalent residues in each protein and includes three strands each from their @sheets, in addition to a connecting loop. The equivalent secondary structure elements in each of these enzymes donate four amino acids forming key hydrogen bonds responsible for the common orientation of the "AMP" moieties of their ATP-ligands. One lysine residue conserved throughout the three families binds the alpha-phosphate in each protein. The common fragments of structure also position some, but not all, of the equivalent residues involved in hydrophobic contacts with the adenine ring. These examples of convergent evolution reinforce the view that different proteins can fold in different ways to produce similar structures locally, and nature can take advantage of these features when structure and function demand it, as shown here for the common mode of ATP-binding by three unrelated proteins.Keywords: allosteric effector-binding site; ATP-dependent enzymes; convergent structural similarities; local structural comparisons; similar ligand-binding sites Adenosine 5"triphosphate (ATP) is necessary for the function of a wide variety of enzymes. Currently, the Brookhaven Protein Data Bank (PDB) (Bernstein et al., 1977) contains atomic coordinates for over 140 X-ray and NMR structures of ATP-dependent proteins solved as complexes mainly with bound ATP-analogues, bound AMP, bound ADP, and in some cases with bound ATP.Several distinct classes of folds of ATP-dependent enzymes have been identified (Schulz, 1992). Acharacteristic feature of these folds is the presence of a P-sheet, parallel or antiparallel, in the vicinity of the ATP-binding site. One class of folds, the classic mononucleotide-binding fold (Schulz & Schirmer, 1974;Rossmann et al., 1975;Schulz et al., 1986), has an ATP-binding site placed at the edge of a parallel P-sheet. Two other classes of folds, the protein kinase family fold (Hanks et al

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Enzyme‐mononucleotide interactions: Three different folds share common structural elements for atp recognition

1998

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“…2 shows a comparison of the aa sequence of DDL from S. lavendulae with those from various bacteria. The amino acids that interact with ATP and D-Ala (30) are conserved except for Leu 320 , which corresponds to Leu 282 of the E. coli DdlB. In some cases, the Leu residue is replaced by Met (Fig.…”

Section: Cloning Of Genes Encoding the Dcs Resistancementioning

confidence: 99%

Self-protection Mechanism in d-Cycloserine-producing Streptomyces lavendulae

Noda

Kawahara

Ichikawa

et al. 2004

Journal of Biological Chemistry

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An antibiotic, D-cycloserine (DCS), inhibits the catalytic activities of alanine racemase (ALR) and D-alanyl-D-alanine ligase (DDL), which are necessary for the biosynthesis of the bacterial cell wall. In this study, we cloned both genes encoding ALR and DDL, designated alrS and ddlS, respectively, from DCS-producing Streptomyces lavendulae ATCC25233. Each gene product was purified to homogeneity and characterized. Escherichia coli, transformed with a pET vector carrying alrS or ddlS, displays higher resistance to DCS than the same host carrying the E. coli ALR-or DDL-encoded gene inserted into the pET vector. Although the S. lavendulae DDL was competitively inhibited by DCS, the K i value (920 M) was obviously higher (40ϳ100-fold) than those for E. coli DdlA (9 M) or DdlB (27 M). The high K i value of the S. lavendulae DDL suggests that the enzyme may be a self-resistance determinant in the DCS-producing microorganism. Kinetic studies for the S. lavendulae ALR suggest that the time-dependent inactivation rate of the enzyme by DCS is absolutely slower than that of the E. coli ALR. We conclude that ALR from DCS-producing S. lavendulae is also one of the self-resistance determinants.

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“…The solution of the crystal structure of E. coli biotin carboxylase 14 in the mid-1990s turned out to be fortuitous in that it became one of the charter members (along with glutathione synthetase, 28 D-Ala-DAla ligase, 29 and succinyl-CoA synthetase 30 ) in the discovery of the ATP-grasp superfamily of enzymes. 31,32 Most, but certainly not all members of this family, catalyze bond formation between a carboxylate and an amino (or thiol) group where the first step involves the hydrolysis of ATP to activate a carboxylate-containing substrate and the second step involves a nucleophilic attack on the carbonyl carbon of the acylphosphate intermediate (Fig.…”

Section: Introductionmentioning

confidence: 99%

The enzymes of biotin dependent CO₂ metabolism: What structures reveal about their reaction mechanisms

2012

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Biotin is the major cofactor involved in carbon dioxide metabolism. Indeed, biotindependent enzymes are ubiquitous in nature and are involved in a myriad of metabolic processes including fatty acid synthesis and gluconeogenesis. The cofactor, itself, is composed of a ureido ring, a tetrahydrothiophene ring, and a valeric acid side chain. It is the ureido ring that functions as the CO 2 carrier. A complete understanding of biotin-dependent enzymes is critically important for translational research in light of the fact that some of these enzymes serve as targets for antiobesity agents, antibiotics, and herbicides. Prior to 1990, however, there was a dearth of information regarding the molecular architectures of biotin-dependent enzymes. In recent years there has been an explosion in the number of three-dimensional structures reported for these proteins. Here we review our current understanding of the structures and functions of biotindependent enzymes. In addition, we provide a critical analysis of what these structures have and have not revealed about biotin-dependent catalysis.

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Vancomycin Resistance: Structure of D-Alanine:D-Alanine Ligase at 2.3 Å Resolution

Cited by 255 publications

References 28 publications

Enzyme‐mononucleotide interactions: Three different folds share common structural elements for atp recognition

Enzyme‐mononucleotide interactions: Three different folds share common structural elements for atp recognition

Self-protection Mechanism in d-Cycloserine-producing Streptomyces lavendulae

The enzymes of biotin dependent CO₂ metabolism: What structures reveal about their reaction mechanisms

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Vancomycin Resistance: Structure of D-Alanine:D-Alanine Ligase at 2.3 Å Resolution

Cited by 255 publications

References 28 publications

Enzyme‐mononucleotide interactions: Three different folds share common structural elements for atp recognition

Enzyme‐mononucleotide interactions: Three different folds share common structural elements for atp recognition

Self-protection Mechanism in d-Cycloserine-producing Streptomyces lavendulae

The enzymes of biotin dependent CO2 metabolism: What structures reveal about their reaction mechanisms

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The enzymes of biotin dependent CO₂ metabolism: What structures reveal about their reaction mechanisms