Crystal structure of a d-aminopeptidase from Ochrobactrum anthropi, a new member of the ‘penicillin-recognizing enzyme’ family

Bompard-Gilles, C.; Remaut, Han; Villeret, Vincent; Prangé, Thierry; Fanuel, Laurence; Delmarcelle, Michaël; Joris, Bernard; Frère, Jean‐Marie; Beeumen, Jozef Van

doi:10.1016/s0969-2126(00)00188-x

Cited by 43 publications

(47 citation statements)

References 41 publications

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“…A loop protruding from the last ␤-barrel interacts with the catalytic module. This (124), the TEM ␤-lactamase of class A (5, 113, 217), the P99 ␤-lactamase of class C (168), the Oxa-10 ␤-lactamase of class D (170), the acyltransferase modules of the D-aminopeptidase DAP (26), and the PBP fusion Spn2x of subclass B4 (173) all adopt the same overall fold, indicating a common ancestral origin. The Streptomyces sp.…”

Section: Group II Sxxk Acyltransferasesmentioning

confidence: 99%

“…The two proteins are related by a P value of 10 Ϫ48 (identity, 36%). Ochrobactrum anthropi produces intracellularly a D-aminopeptidase, DAP, which acts on D-alanine amide and peptides with a Dalanine residue at the amino end (11,26). The carbonyl side only of the scissile bond is borne by a D-configured carbon atom.…”

Section: Group II Sxxk Acyltransferasesmentioning

confidence: 99%

“…strain R61 are distantly related by a P value of 3 ϫ 10 Ϫ18 (identity, 26%),yet the two polypeptides adopt the same fold (26). The noncatalytic carboxy-terminal module of the peptidase DAP comprises two eight-stranded ␤-barrels.…”

Section: Group II Sxxk Acyltransferasesmentioning

confidence: 99%

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Biochemistry and Comparative Genomics of SxxK Superfamily Acyltransferases Offer a Clue to the Mycobacterial Paradox: Presence of Penicillin-Susceptible Target Proteins versus Lack of Efficiency of Penicillin as Therapeutic Agent

Goffin

Ghuysen

2002

Microbiol Mol Biol Rev

179

213

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The bacterial acyltransferases of the SxxK superfamily vary enormously in sequence and function, with conservation of particular amino acid groups and all-α and α/β folds. They occur as independent entities (free-standing polypeptides) and as modules linked to other polypeptides (protein fusions). They can be classified into three groups. The group I SxxK d,d-acyltransferases are ubiquitous in the bacterial world. They invariably bear the motifs SxxK, SxN(D), and KT(S)G. Anchored in the plasma membrane with the bulk of the polypeptide chain exposed on the outer face of it, they are implicated in the synthesis of wall peptidoglycans of the most frequently encountered (4→3) type. They are inactivated by penicillin and other β-lactam antibiotics acting as suicide carbonyl donors in the form of penicillin-binding proteins (PBPs). They are components of a morphogenetic apparatus which, as a whole, controls multiple parameters such as shape and size and allows the bacterial cells to enlarge and duplicate their particular pattern. Class A PBP fusions comprise a glycosyltransferase module fused to an SxxK acyltransferase of class A. Class B PBP fusions comprise a linker, i.e., protein recognition, module fused to an SxxK acyltransferase of class B. They ensure the remodeling of the (4→3) peptidoglycans in a cell cycle-dependent manner. The free-standing PBPs hydrolyze d,d peptide bonds. The group II SxxK acyltransferases frequently have a partially modified bar code, but the SxxK motif is invariant. They react with penicillin in various ways and illustrate the great plasticity of the catalytic centers. The secreted free-standing PBPs, the serine β-lactamases, and the penicillin sensors of several penicillin sensory transducers help the d,d-acyltransferases of group I escape penicillin action. The group III SxxK acyltransferases are indistinguishable from the PBP fusion proteins of group I in motifs and membrane topology, but they resist penicillin. They are referred to as Penr protein fusions. Plausible hypotheses are put forward on the roles that the Penr protein fusions, acting as l,d-acyltransferases, may play in the (3→3) peptidoglycan-synthesizing molecular machines. Shifting the wall peptidoglycan from the (4→3) type to the (3→3) type could help Mycobacterium tuberculosis and Mycobacterium leprae survive by making them penicillin resistant

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Section: Group II Sxxk Acyltransferasesmentioning

confidence: 99%

Section: Group II Sxxk Acyltransferasesmentioning

confidence: 99%

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Biochemistry and Comparative Genomics of SxxK Superfamily Acyltransferases Offer a Clue to the Mycobacterial Paradox: Presence of Penicillin-Susceptible Target Proteins versus Lack of Efficiency of Penicillin as Therapeutic Agent

Goffin

Ghuysen

2002

Microbiol Mol Biol Rev

179

213

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“…The crucial role of Ser-61 (and Lys-64, which are both part of the S-X-X-K motif) for catalysis has been confirmed by mutagenesis studies [265]. The crystal structure of DAP has been determined to 1.9 A resolution [266]. This aminopeptidase folds into three domains, A, B, and C. The N-terminal domain (domain A) contains all catalytic residues and is structurally highly analogous R61 DD-carboxypeptidase and serine b-lactamases.…”

Section: D-selective A-h-a-amino Acid Amide Hydrolasementioning

confidence: 86%

Hydrolysis of Amides

Sonke

Kaptein

2012

Enzyme Catalysis in Organic Synthesis

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“…The three-dimensional structures of D-Ala-D-Ala carboxypeptidase B from Streptomyces sp. R61 and D-aminopeptidase from Ochrobactrum anthropi have been described in the literature (13,31). A previous study described that the loop in the C-terminal domain (L3 loop) was responsible for their different substrate specificities (16).…”

Section: Discussionmentioning

confidence: 99%

One-Pot Synthesis of Diverse dl -Configuration Dipeptides by a Streptomyces d -Stereospecific Amidohydrolase

Arima

Usuki²,

Hatanaka³

et al. 2011

Appl Environ Microbiol

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The synthesis of diverse DL-configuration dipeptides in a one-pot reaction was demonstrated by using a function of the aminolysis reaction of a D-stereospecific amidohydrolase from Streptomyces sp., a clan SE, S12 family peptidase categorized as a peptidase with D-stereospecificity. The enzyme was able to use various aminoacyl derivatives, including L-aminoacyl derivatives, as acyl donors and acceptors. Investigations of the specificity of the peptide synthetic activity revealed that the enzyme preferentially used D-aminoacyl derivatives as acyl donors. In contrast, L-amino acids and their derivatives were preferentially used as acyl acceptors. Consequently, the synthesized dipeptides had a DL-configuration when D-and L-aminoacyl derivatives were mixed in a one-pot reaction. This report also describes that the enzyme produced cyclo(D-Pro-L-Arg), a specific inhibitor of family 18 chitinase, with a conversion rate for D-Pro benzyl ester and L-Arg methyl ester to cyclo(D-Pro-L-Arg) of greater than 65%. Furthermore, based on results of cyclo(D-Pro-L-Arg) synthesis, we propose a reaction mechanism for cyclo(D-Pro-L-Arg) production.Peptides incorporating D-amino acids in nature were found to be antimicrobial compounds and signal molecules. They are expected to increase the functional variety and applications of peptides (11,12,33,38,42). For example, alitame, L-Asp-DAla fenchyl ester, is known to be over a thousand times sweeter than sucrose (57). Cyclo(D-Pro-L-Arg) is known to act as a specific inhibitor of family 18 chitinase. It is also regarded as the ideal lead compound for the development of antifungal reagents and insecticides (25). In fact, D-amino-acid-containing peptides have been produced through organic synthesis (21,44), and the complicated reaction steps and the racemization of amino acids present difficulties for organic synthesis. Therefore, enzyme-catalyzed peptide synthesis is well recognized as an alternative method for chemical synthesis. Recent reports have described enzymatic synthesis using peptidase (30, 32), esterase (52), aminoacyltransferase (53), and D-alanine-D-alanine ligase (48). Among them, aminolysis reactions of serine peptidases have increasingly attracted attention as tools for the synthesis of peptides because of their obviation of expensive additives such as ATP, their simple kinetics, and their ease of handling (1,36).In a previous study, we obtained two D-stereospecific amidohydrolases from Streptomyces spp. and confirmed that they have the function of an aminolysis reaction (

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Crystal structure of a d-aminopeptidase from Ochrobactrum anthropi, a new member of the ‘penicillin-recognizing enzyme’ family

Cited by 43 publications

References 41 publications

Biochemistry and Comparative Genomics of SxxK Superfamily Acyltransferases Offer a Clue to the Mycobacterial Paradox: Presence of Penicillin-Susceptible Target Proteins versus Lack of Efficiency of Penicillin as Therapeutic Agent

Biochemistry and Comparative Genomics of SxxK Superfamily Acyltransferases Offer a Clue to the Mycobacterial Paradox: Presence of Penicillin-Susceptible Target Proteins versus Lack of Efficiency of Penicillin as Therapeutic Agent

Hydrolysis of Amides

One-Pot Synthesis of Diverse dl -Configuration Dipeptides by a Streptomyces d -Stereospecific Amidohydrolase

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