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首页> 外文期刊>Acta crystallographica. Section D, Structural biology. >Structure and mechanism of piperideine-6-carboxylate dehydrogenase from Streptomycesclavuligerus
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Structure and mechanism of piperideine-6-carboxylate dehydrogenase from Streptomycesclavuligerus

机译：的结构和机制piperideine-6-carboxylate脱氢酶从

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摘要

The core of beta-lactam antibiotics originates from amino acids of primarymetabolism in certain microorganisms. beta-Lactam-producing bacteria, includingStreptomyces clavuligerus, synthesize the precursor of the amino acid alpha-amino-adipic acid by the catabolism of lysine in two steps. The second reaction, theoxidation of piperideine-6-carboxylate (or its open-chain form alpha-aminoadipatesemialdehyde) to alpha-aminoadipic acid, is catalysed by the NAD~+-dependentenzyme piperideine-6-carboxylate dehydrogenase (P6CDH). This structuralstudy, focused on ligand binding and catalysis, presents structures of P6CDHfrom S. clavuligerus in its apo form and in complexes with the cofactor NAD~+,the product a-aminoadipic acid and a substrate analogue, picolinic acid. P6CDHadopts the common aldehyde dehydrogenase fold, consisting of NAD-binding,catalytic and oligomerization domains. The product binds in the oxyanion hole,close to the catalytic residue Cys299. Clear density is observed for the entirecofactor, including the nicotinamide riboside, in the binary complex. NAD~+binds in an extended conformation with its nicotinamide ring overlapping withthe binding site of the carboxylate group of the product, implying that theconformation of the cofactor may change during catalysis. The binding site ofthe substrate analogue overlaps with that of the product, suggesting that thecyclic form of the substrate, piperideine-6-carboxylate, may be accepted as asubstrate by the enzyme. The catalytic mechanism and the roles of individualresidues are discussed in light of these results.
机译：beta-lactam抗生素产生的核心primarymetabolism在特定的氨基酸微生物。includingStreptomyces clavuligerus,合成的前体氨基酸alpha-amino-adipic酸的分解代谢赖氨酸在两个步骤。theoxidation piperideine-6-carboxylate(或其碳链形式alpha-aminoadipatesemialdehyde)alpha-aminoadipic酸,是催化的NAD ~ + -dependentenzyme piperideine-6-carboxylate脱氢酶(P6CDH)。集中在配体结合和催化、礼物结构的P6CDHfrom s clavuligerusapo形式和复合物的代数余子式NAD ~ +,产品a-aminoadipic酸和一个底物类似物,吡啶甲酸。常见的醛脱氢酶折叠,包括NAD-binding、催化和寡聚化域。oxyanion洞,接近催化残基Cys299。entirecofactor,包括烟酰胺核苷,在二进制复杂。扩展的构象与烟酰胺环重叠的结合位点羧酸盐集团的产品,这意味着theconformation代数余子式的可能变化催化。模拟重叠与产品,这表明thecyclic衬底,piperideine-6-carboxylate,可能被接受asubstrate的酶。和individualresidues的角色进行了讨论根据这些结果。

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