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At least 19 recordsLinked to original sources
PubMed1987

Kinetics and mechanism of the serine beta-lactamase catalyzed hydrolysis of depsipeptides.

Steady-state kinetic parameters have been determined for the hydrolysis of a series of acyclic depsipeptides (ester analogues of acyl-D-alanyl-D-alanine peptides) catalyzed by representative class C (Enterobacter cloacae P99) and class A (Bacillus cereus I, TEM-2, and Staphylococcus aureus PC1) beta-lactamases. The best of these substrates, and the one most used in this work, was m-[[(phenylacetyl)-glycyl]oxy]benzoic acid, whose rates of cleavage could be followed spectrophotometrically. The P99 enzyme also catalyzed the methanolysis of these substrates in aqueous methanol solutions. Quantitative evaluation of the effects of methanol on the kinetics of the competing hydrolysis and methanolysis reactions, and on the product distribution, supports a reaction mechanism involving an acyl-enzyme intermediate whose formation is rate-determining under conditions of substrate saturation. Consideration of the variation of these kinetic parameters with the structure of the depsipeptides and comparison with the analogous parameters for bicyclic beta-lactam substrates suggest that a variety of substrate binding modes exist on this enzyme. The class A enzymes, B. cereus beta-lactamase I and the TEM-2 beta-lactamase, catalyze depsipeptide and benzylpenicillin hydrolyses but not methanolysis. The acyl-enzyme derived from both types of substrate is thus shielded from external nucleophiles; the shielding is therefore not an effect, direct or indirect, of the thiazolidinyl group in the penicilloyl-enzyme. The class A beta-lactamase of the PC1 plasmid of S. aureus is distinctly different from the above two representatives of that class, in that it does catalyze methanolysis of depsipeptides (but not of benzylpenicillin). The methanolysis kinetics suggest that deacylation is rate-determining at saturation, a conclusion supported by the demonstration of an intermediate during the hydrolysis of m-[[(phenylacetyl)glycyl]oxy]benzoate, subsequent to leaving-group departure. The beta-lactamases have thus been shown to catalyze the hydrolysis of specific depsipeptides with comparable facility to that demonstrated by D-alanyl-D-alanine carboxypeptidase/transpeptidases. The former enzymes, however, differ in being unable to cleave the analogous peptides.

Bacillus cereus↗
PubMedDate not supplied

Depsipeptide analogues of elastin repeating sequences: synthesis.

Depsipeptide analogues of peptide sequences can help in elucidating the role of specific hydrogen bonds in determining the conformation in peptides. The repeating pentapeptide and hexapeptide sequences of elastin have been suggested to contain a type II beta-turn with a 4----1 hydrogen bond. Depsipeptide analogues of the repeating sequences of elastin in which this 4----1 hydrogen bond cannot exist were synthesized. A fragment condensation approach was employed in which the depsipeptide ester bond was introduced early in the synthesis. This approach proved to be effective, although the increased lability of the depsipeptide ester bond resulted in side products and low yields in some reactions.

Amino Acid Sequence↗
PubMedDate not supplied

Depsipeptide analogues of elastin repeating sequences: conformational analysis.

In this work the effect of elimination of a specific hydrogen bond on the conformation of the repeating peptides of elastin was studied. These repeating sequences are the pentapeptide Val-Pro-Gly-Val-Gly and the hexapeptide Val-Ala-Pro-Gly-Val-Gly. These sequences have been proposed to occur in a beta-turn conformation with a hydrogen bond involving the amide NH of the internal valine residue and the carbonyl oxygen of the residue preceding proline. In the depsipeptide analogues studied in this work, this 4-1 beta-turn hydrogen bond cannot occur. We studied the depsipeptide sequences Val-Pro-Gly-Hiv-Gly and Val-Ala-Pro-Gly-Hiv-Gly (Hiv denotes S-alpha-hydroxyisovaleric acid, the hydroxy acid analogue of valine), as well as the peptide sequences Val-Pro-Gly-Val-Gly and Val-Ala-Pro-Gly-Val-Gly. Compounds studied included sequences with the Boc and benzyl ester protecting groups, derivatives with the acetyl and N-methylamide end groups and polymers of the above sequences. Our conclusions are based on a comparison of depsipeptides with analogous peptides. Conformational analysis was carried out by nmr, CD, and ir spectroscopy. We propose that in the repeating sequences of elastin an equilibrium exists between a gamma-turn structure and a beta-turn structure in the Pro-Gly segment resulting in a structure that combines flexibility with strong conformational preferences. The C7 involves the amide NH of the internal glycine and the carbonyl oxygen of the residue preceding proline. In the N-methylamide derivatives a similar equilibrium exists in the Gly-Val-Gly segment. In the depsipeptides the beta-turn cannot occur and only the gamma-turn is seen. In the polydepsipeptides the major conformational feature is a type I beta-turn involving Gly5 NH and Pro CO.

Amino Acid Sequence↗
PubMed1985

The role of the cyclic depsipeptide rings in antibiotics.

The physical and biological roles of the cyclic depsipeptides of actinomycin, quinomycin and triostin antibiotic families are proposed by examining the crystal structures of d(GC)-actinomycin D and d(CGTACG)-triostin A. The analyses suggest that not only are DNA-amino acid hydrogen-bonding and chromophore-base pair stacking crucially important for DNA-antibiotic interaction, but also that the unique structure of the cyclic depsipeptides (the perfect hydrophobic character of the inner surface) is equally necessary to insure that these interactions are directed, unambiguous and screened from interference by solvent. Beyond this, the characteristic nature of the outer surfaces suggests a further hypothesis for the biological role of the cyclic depsipeptide rings; when the antibiotics bind in the region around the pause or rho-dependent termination sites on the DNA, the drugs actually terminate transcription by RNA polymerase and cause release of a premature RNA transcript. Termination is likely because the antibiotics carry five to six consecutive apparent A/T sequences on the surface of the cyclic depsipeptide rings, thus presenting a deceptive termination signal to the polymerase.

Anti-Bacterial Agents↗
PubMed1989

Didemnin B. Conformation and dynamics of an antitumour and antiviral depsipeptide studied in solution by 1H and 13C. n.m.r. spectroscopy.

The solution conformation of didemnin B, the most potent member of a family of depsipeptides that shows antitumour, antiviral, and immunosuppressive activity, has been studied in chloroform solution using n.m.r. spectroscopy. 1H and 13C spectra have been assigned from analysis of a number of two-dimensional homonuclear and heteronuclear chemical shift correlation experiments which confirm the recently corrected primary structure of the molecule. The conformation of the peptide has been deduced from measurements of the temperature dependence of the NH chemical shifts, analysis of coupling constant data and primarily through NOE effects observed in the rotating frame. Interproton distance bounds determined from a quantitative analysis of the ROE data provide 41 constraints from which a family of closely related structures were calculated using distance geometry algorithms. A type II beta-turn involving residues Thr6, Leu7, and Pro8 is well represented in the computed conformers as is a hydrogen bonding interaction between the NH of Leu3 and the carbonyl oxygen of Thr6. This latter interaction causes the linear portion of the structure to fold back over the depsipeptide ring, imparting to it a degree of structural stability as well as giving the molecule a somewhat globular character. Only one transannular hydrogen bond, between Ist1 NH and Leu3 carbonyl, stabilizes the conformation of the depsipeptide, which has an irregular non-planar configuration. The small temperature coefficients (less than 2.0 x 10(-3) ppm/degrees C) for the NHs of Ist1 and Leu3 are consistent with their involvement in these hydrogen bonding interactions. We find that many of the structural features observed in the crystalline form of didemnin B are conserved in solution. Analysis of the 13C spin-lattice relaxation rates of the protonated carbons reveals small variations in effective correlation times at specific sites in the molecule. The data suggests that the peptide segment encompassing residues Leu3 through to Thr6 is in a more motionally restricted part of the structure.

Amino Acid Sequence↗
PubMed1978

Utilization of a depsipeptide substrate for trapping acyl-enzyme intermediates of penicillin-sensitive D-alanine carboxypeptidases.

The penicillin-sensitive D-alanine carboxypeptidases of Bacillus subtilis, Escherichia coli, and Staphylococcus aureus catalyzed the hydrolysis of the D-lactic acid residue from the depsipeptide diacetyl-L-lysyl-D-alanyl-D-lactic acid. The ester substrate was hydrolyzed faster than the peptide analogue, diacetyl-L-lysyl-D-alanyl-D-alanine, by the B. subtilis (15-fold) and E. coli (4-fold) carboxypeptidases, presumably because acylation (k(2)), which is the rate-limiting step of the peptidase reaction, occurred more rapidly during cleavage of the ester bond than during cleavage of the amide bond. No rate acceleration was observed with the S. aureus carboxypeptidase for which deacylation (k(3)) is already the rate-determining step with the peptide substrate. The efficiency of utilization of the depsipeptide (V(max)/K(m)) was greatly enhanced (19- to 147-fold) for all three enzymes. After incubation of the B. subtilis carboxypeptidase and [(14)C]diacetyl-L-lysyl-D-alanyl-D-lactic acid at pH 5.0 and lowering of the pH to 3.0, a radioactive acyl-enzyme intermediate containing 0.43 mol of substrate per mol of enzyme was isolated by Sephadex G-50 chromatography. After acetone precipitation, the acyl group of the denatured acyl-enzyme complex appeared to be bound to the protein by an ester bond. Acyl enzymes were also detected for the S. aureus and E. coli carboxypeptidases after sodium dodecyl sulfate/polyacrylamide gel electrophoresis and fluorography of enzyme incubated with [(14)C]depsipeptide and precipitated with acetone.

Acylation↗
PubMed1988

Crystal and molecular structure of didemnin B, an antiviral and cytotoxic depsipeptide.

Didemnin B, a highly active depsipeptide isolated from a Caribbean tunicate, crystallizes from chloroform/benzene in the orthorhombic space group C2221, with cell parameters a = 14.990 +/- 0.003 A, b = 22.574 +/- 0.004 A, c = 41.112 +/- 0.009 A, V = 13911.7 A3 at 138 K and a calculated density of 1.143 g/cm3 based on C57H89N7O15, 1.5C6H6.H2O and eight formula units per cell. The overall agreement factor R = 0.052 for 7699 reflections, 20 theta max = 150 degrees, Cu K-alpha radiation. The structure determination revealed that didemnin B contains an isostatine residue instead of a statine residue. The conformation of the 23-membered depsipeptide ring is stabilized by one transannular hydrogen bond. The ring does not show the antiparallel beta-pleated-sheet structure but, instead, has a fold in the shape of a bent figure-eight. The linear peptide moiety, containing N-methylleucine and lactylproline, forms a beta (II)-bend and is folded back toward the cyclic backbone, giving the overall molecule a globular character. Comparison with the structure of cyclosporin A shows distinct stereochemical differences between the two molecules. It is suggested that didemnin B and cyclosporin A are unlikely to have a common receptor binding site.

Antiviral Agents↗
PubMed1985

Clostridium histolyticum collagenase: development of new thio ester, fluorogenic, and depsipeptide substrates and new inhibitors.

A new series of thio ester, depsipeptide, and peptide substrates have been synthesized for the bacterial enzyme Clostridium histolyticum collagenase. The hydrolysis of the depsipeptide substrate was followed on a pH stat, and thio ester hydrolysis was measured by inclusion of the chromogenic thiol reagent 4,4'-dithiopyridine in the assay mixture. The best thio ester substrate, Boc-Abz-Gly-Pro-Leu-SCH2CO-Pro-Nba, had a kcat/KM of 63 000 M-1 s-1, while several shorter thio ester sequences were inactive as substrates. In general, the peptide analogues of all the reactive thio ester substrates were shown to be hydrolyzed 5-10 times faster by collagenase. In one case (Z-Gly-Pro-Leu-Gly-Pro-NH2) where a comparison was made, the peptide substrate was respectively 8- and 106-fold more readily hydrolyzed than the corresponding thio ester and ester substrates. Cleavages of the two fluorescence-quench substrates Abz-Gly-Pro-Leu-Gly-Pro-Nba and Abz-Gly-Pro-Leu-SCH2CO-Pro-Nba could be easily followed fluorogenically since a 5-10-fold increase in fluorescence occurred upon hydrolysis. The fluorescent peptide substrate is the best synthetic substrate known for C. histolyticum collagenase with a kcat/KM value of 490 000 M-1 s-1. A series of new reversible inhibitors were developed by the attachment of zinc ligating groups (hydroxamic acid, carboxymethyl, and thiol) to various peptide sequences specific for C. histolyticum collagenase. The shorter peptides designed to bind to either the P3-P1 or P1'-P3' subsites were poor to moderate inhibitors. The thiol HSCH2CH2CO-Pro-Nba had the lowest K1 (0.02 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Clostridium↗
PubMed1989

Beta-lactamase-catalyzed aminolysis of depsipeptides: proof of the nonexistence of a specific D-phenylalanine/enzyme complex by double-label isotope trapping.

The steady-state kinetics of the Enterobacter cloacae P99 beta-lactamase-catalyzed aminolysis of the depsipeptide m-[[(phenylacetyl)glycyl]oxy]benzoic acid by D-phenylalanine were consistent with an ordered sequential mechanism with D-phenylalanine binding first [Pazhanisamy, S., Govardhan, C. P., & Pratt, R. F. (1989) Biochemistry (first of three papers in this issue)]. In terms of this mechanism, the kinetics data required that in 20 mM MOPS buffer, pH 7.5, the dissociation constant of the initially formed enzyme/D-phenylalanine complex be around 1.3 mM; at pH 9.0 in 0.1 M carbonate buffer, the complex should be somewhat more stable. Attempts to detect this complex in a binary mixture by spectroscopic methods (fluorescence, circular dichroic, and nuclear magnetic resonance spectra) failed. Kinetic methods were also unsuccessful--the presence of 20 mM D-phenylalanine did not appear to affect beta-lactamase activity nor inhibition of the enzyme by phenylmethanesulfonyl fluoride, phenylboronic acid, or (3-dansylamidophenyl)boronic acid. Equilibrium dialysis experiments appeared to indicate that the dissociation constant of any binary enzyme/D-phenylalanine complex must be somewhat higher than the kinetics allowed (greater than 2 mM). Since the kinetics also required that, at high depsipeptide concentrations, and again with the assumption of the ordered sequential mechanism, the reaction of the enzyme/D-phenylalanine complex to aminolysis products be faster than its reversion to enzyme and D-phenylalanine, a double-label isotope-trapping experiment was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Circular Dichroism↗
PubMed1991

Evidence from a mutant beta-lactamase for the mechanism of beta-lactamase-catalysed depsipeptide aminolysis.

The Ser-70----Gly mutant of the TEM-1 beta-lactamase, where the active-site serine hydroxy group has been lost, does not catalyse the hydrolysis of either benzylpenicillin or N-(phenylacetyl)glycyl depsipeptides. This is as would be expected for a double-displacement mechanism where the Ser-70 becomes acylated at an intermediate stage. Further, however, the mutant enzyme, unlike the wild-type, does not catalyse aminolysis of depsipeptides by D-phenylalanine. If the active site is not structurally disrupted by the mutation, this result shows that Ser-70 is necessary for the aminolysis reaction and implies that this reaction, like the hydrolysis, proceeds by way of an acyl-(serine)-enzyme intermediate. Although physical evidence suggests that the mutant enzyme does not have a structure in solution identical with that of the wild-type, the mutant does still bind beta-lactam substrates. The latter result suggests sufficient conservation of the active-site structure for the major conclusion above to hold.

Amines↗
PubMed1979

The identification of depsipeptides by chemical ionisation mass spectroscopy.

The chemical ionisation mass spectra of seven naturally occurring depsipeptides and some of their permethylated derivatives have been measured. The primary ionisation process involves an ester group and not an amide or other functionality. It probably occurs randomly when the molecule contains more than one ester link. Unlike electron impact mass spectra, those obtained under chemical ionisation conditions gave sequence information for all of the depsipeptides examined or their permethylated derivatives. A mechanism for the primary fragmentation is proposed.

Anti-Bacterial Agents↗
PubMed1992

Dolastatin 15, a potent antimitotic depsipeptide derived from Dolabella auricularia. Interaction with tubulin and effects of cellular microtubules.

Dolastatin 15, a seven-subunit depsipeptide derived from Dolabella auricularia, is a potent antimitotic agent structurally related to the antitubulin agent dolastatin 10, a five-subunit peptide obtained from the same organism. We have compared dolastatin 15 with dolastatin 10 for its effects on cells grown in culture and on biochemical properties of tubulin. The IC50 values for cell growth were obtained for dolastatin 15 with L1210 murine leukemia cells, human Burkitt lymphoma cells, and Chinese hamster ovary (CHO) cells (3, 3, and 5 nM with the three cell lines, respectively). For dolastatin 10, IC50 values of 0.4 and 0.5 nM were obtained with the L1210 and CHO cells, respectively. At toxic concentrations dolastatin 15 caused the leukemia and lymphoma cells to arrest in mitosis. In the CHO cells both dolastatin 15 and dolastatin 10 caused moderate loss of microtubules at the IC50 values and complete disappearance of microtubules at concentrations 10-fold higher. Despite its potency and the loss of microtubules in treated cells, the interaction of dolastatin 15 with tubulin in vitro was weak. Its IC50 value for inhibition of glutamate-induced polymerization of tubulin was 23 microM, as compared to values of 1.2 microM for dolastatin 10 and 1.5 microM for vinblastine. Dolastatin 10 noncompetitively inhibits the binding of vincristine to tubulin, inhibits nucleotide exchange, stabilizes the colchicine binding activity of tubulin, and inhibits tubulin-dependent GTP hydrolysis (Bai et al., Biochem Pharmacol 39: 1941-1949, 1990; Bai et al. J Biol Chem 265: 17141-17149, 1990). Only the latter reaction was inhibited by dolastatin 15. Nevertheless, its structural similarity to dolastatin 10 indicates that dolastatin 15 may bind weakly in the "vinca domain" of tubulin (a region of the protein we postulate to be physically close to but not identical with the specific binding site of vinca alkaloids and maytansinoids), presumably in the same site as dolastatin 10 (the "peptide site").

Amino Acid Sequence↗
PubMed1988

Phase I clinical and pharmacokinetic investigation of didemnin B, a cyclic depsipeptide.

Didemnin B (NSC-325319), a cyclic depsipeptide isolated from a marine tunicate, has been evaluated in a Phase I trial. The drug was administered in a single intravenous infusion in 150 cm3 of normal saline every 30 min given every 28 days. Forty-three patients received 80 courses of the drug at doses ranging from 0.14 to 4.51 mg/m2. The dose-limiting toxicity was nausea and vomiting which began during or shortly after the infusion and was of variable duration. This toxicity was somewhat ameliorated by pretreatment with an aggressive antiemetic regimen. Mild hepatic toxicity also occurred with mild elevations of transaminases and bilirubin. One patient experienced an allergic reaction during his second infusion, characterized by chills, diaphoresis, flushing and hypotension. No objective anti-tumor response was seen during this trial. The recommended dose for Phase II studies on a single-dose schedule is 2.67 mg/m2 without prophylactic antiemetics and 3.47 mg/m2 if an antiemetic regimen is used. Preliminary pharmacokinetics suggest that didemnin B is sequestered or rapidly converted to a metabolite not identified by the antibody used in the radioimmunoassay. Further evaluation will be performed during Phase II studies.

Adult↗
PubMedDate not supplied

In vitro evaluation of ramoplanin (A16686 or MDL62198). A new depsipeptide complex for potential topical use.

Ramoplanin, a new depsipeptide complex, was found to be 4- to 8-fold more active than vancomycin against all Gram-positive species (500 strains). Similarly, ramoplanin was both more active and had an additional spectrum compared to mupirocin (formerly pseudomonic acid) against Bacillus spp., Corynebacterium jeikeium, enterococci and Listeria monocytogenes. Mupirocin-resistant Staphylococcus spp. strains (less than 1%) were identified in these organisms collected from over 40 medical centers in the United States. These strains (S. capitis and S. saprophyticus) were susceptible to ramoplanin at 0.25 micrograms/ml or less. The three tested antimicrobial agents were not effective against Gram-negative organisms (20 species tested). Ramoplanin was bactericidal and MICs were not adversely influenced by high (greater than or equal to 10(7) CFU/ml) inoculum concentrations. Because ramoplanin has previously shown promise as a topical drug, these in vitro results further substantiate its wide spectrum, potency, and potential clinical usefulness as mupirocin-resistant staphylococci and other Gram-positive species become more prevalent.

Administration, Cutaneous↗
PubMed1992

Crystal and molecular structure of the depsipeptide ionophore hexadecaisoleucinomycin, cyclo-[(D-Ile-L-Lac-L-Ile-D-Hyi)4-] (C80H136N8O24).

The crystal structure of a synthetic depsipeptide ionophore hexadecaisoleucinomycin, cyclo [-(D-Ile-L-Lac-L-Ile-D-Hyi)4-] (C80H136N8O24), has been determined by single crystal x-ray diffraction techniques. The crystals are orthorhombic, space group P2(1)2(1)2(1), number of molecules per unit cell z = 4, and cell parameters a = 11,195, b = 17.853, c = 54.835 A. The values of the standard (R) and weighted (Rw) discrepancy factors after refinement are 0.122 and 0.135, respectively. The structure is characterized by an elongated bracelet form with a twofold axis of pseudosymmetry. It is stabilized by eight intramolecular 4----1 hydrogen bonds between the amide C = O and N - H groups. The ester carbonyls are directed toward the inside of the molecule, their oxygen atoms forming an ellipsoidal internal cavity. The side chains are located on the molecular periphery. The conformational states of hexadecaisoleucinomycin in solution are discussed in the light of the data obtained.

Amino Acid Sequence↗
PubMed1989

Preparative reversed-phase high-performance liquid chromatography in the synthesis of viscosin, a cyclic depsipeptide.

The importance of peptides in biochemical research and the facility with which they can be prepared by solid-phase techniques highlights the need for continuing research in the chromatographic purification of these molecules on a preparative scale. In this regard, synthesis of the cyclic depsipeptide antibiotic, viscosin, has provided the opportunity to demonstrate the use of radial compression cartridge technology in the reversed-phase purification of three key peptide intermediates on a scale of several hundred milligrams. Superior resolution of linear and cyclic peptide mixtures on a Bondapak C18 radial compression cartridge by using an aqueous acetonitrile solvent system containing 0.1% trifluoroacetic acid contributed significantly to the first total synthesis of viscosin, and demonstrates the applicability of this system to the purification of peptide mixtures.

Amino Acid Sequence↗
PubMed1986

Activity of copper-substituted carboxypeptidase A toward oligopeptides and depsipeptides.

Cu(II)-substituted carboxypeptidase A catalyzes the hydrolysis of oligopeptides and their depsipeptide (ester) analogues. Stopped-flow fluorescence assays demonstrate that relative to the zinc enzyme the Cu enzyme can have kcat/Km values up to 24% toward esters but only up to 2.5% toward the corresponding peptides. Adding Zn(II) to the copper enzyme reveals a slow exchange process that correlates with an increase in peptidase activity and with changes in the Cu(II) electron paramagnetic resonance spectra. Low concentrations of 1,10-phenanthroline (OP) (0.1-2.5 microM) markedly increase activity toward furanacryloyl-Phe-Phe (up to 8% of the zinc enzyme), but higher concentrations inhibit, resulting in complete inhibition at 0.8 mM OP. The non-metal-binding, hydrophobic analogues m- and p-phenanthroline are only activators of peptide hydrolysis, even at 1 mM. Activation is likely due to a modifier binding to a hydrophobic locus and either displacing an inhibitory peptide binding mode or inducing a conformational change in the active site.

Carboxypeptidases↗
PubMed1989

Beta-lactamase-catalyzed aminolysis of depsipeptides: amine specificity and steady-state kinetics.

beta-Lactamases catalyze not only the hydrolysis but also the aminolysis of certain depsipeptides [Pratt, R. F., & Govardhan, C. P. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 1302-1306]. This paper explores further the specificity of the aminolysis reaction with respect to the structure of the amine and also the steady-state kinetics of the reaction. The amines preferred by the class C beta-lactamase of Enterobacter cloacae P99 appear to be aromatic D-alpha-amino acids. The general order of substrate effectiveness at pH 7.5 appears to be aromatic D-alpha-amino acids greater than large aliphatic D-alpha-amino acids greater than small aliphatic D-alpha-amino acids approximately small aliphatic L-alpha-amino acids greater than large L-alpha-amino acids. Charges on the aliphatic side chains seem unimportant. Ineffective as acyl acceptors were beta-amino acids, alpha-amino phosphonic acids, and, in general, amines, including amino acid carboxyl derivatives and peptides. There is thus strong evidence for specific interaction between the amine and the enzyme. A detailed kinetics study was made of the P99 beta-lactamase-catalyzed aminolysis of m-[[(phenylacetyl)glycyl]oxy]benzoic acid by D-phenylalanine. The steady-state kinetics were complex because of the presence of parallel enzyme-catalyzed hydrolysis and aminolysis reactions. An empirical rate equation was obtained for the total reaction. This has important elements in common with that previously found for the aminolysis of specific peptides by the DD-peptidases of various Streptomyces strains [e.g., Frere, J.-M., Ghuysen, J.-M., Perkins, H.R., & Nieto, M. (1973) Biochem. J. 135, 483-492].(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗