Staphylococcus aureus produces staphyloxanthin,a C30 carotenoid with golden color,as an antioxidant to promote bacterial resistance to reactive oxygen species.The biosynthesis pathway of staphyloxanthin involves a ser...Staphylococcus aureus produces staphyloxanthin,a C30 carotenoid with golden color,as an antioxidant to promote bacterial resistance to reactive oxygen species.The biosynthesis pathway of staphyloxanthin involves a series of catalytic enzymes.Aldehyde dehydrogenase(AldH)is a dehydrogenase recently identified to convert 4,4’-diaponeurosporenaldehyde into 4,4’-diaponeurosporenoic acid during staphyloxanthin biosynthesis.Here,we present the crystallographic structures of apo-and holo-forms of S.aureus AldH.The dimeric enzyme contains a unique C-terminal helix,which resembles a“gatekeeper”helix found in human membrane-bound fatty aldehyde dehydrogenase(FALDH).Particularly,the helix adopts“open”and“closed”conformations in apo-and holo-AldH,respectively,to control the access of the substrate tunnel.Mutagenesis in combination with in vitro and in vivo activity assays identifies several residues essential for S.aureus AldH substrate recognition and enzyme catalytic turnover.Our results provide insights into substrate recognition of S.aureus AldH toward polyunsaturated long-chain aldehydes at atomic resolution.展开更多
Enzymes are biomacromolecules responsible for the abundant chemical biotransformations that sustain life. Recently, biochemists have discovered that multiple conformations and numerous parallel paths are involved duri...Enzymes are biomacromolecules responsible for the abundant chemical biotransformations that sustain life. Recently, biochemists have discovered that multiple conformations and numerous parallel paths are involved during the processes catalyzed by enzymes. It is plausible that the entire macromolecular scaffold is involved in catalysis via cooperative motions that result in incredible catalytic efficiency. Moreover, some enzymes can very strongly bind the transition state with an association constant of up to 1024 M-1, suggesting that covalent bond formation is a possible process during the conversion of the transition state in enzyme catalysis, in addition to the concatenation of noncovalent interactions. Supramolecular chemistry provides fundamental knowledge about the relationships between the dynamic structures and functions of organized molecules. By tak-ing advantage of supramolecular concepts, numerous supramolecular enzyme mimics with complex and hierarchical structures have been designed and investigated. Through the study of supramolecular enzyme models, a great deal of information to aid our understanding of the mechanism of catalysis by natural enzymes has been acquired. With the development of supramolec-ular artificial enzymes, it is possible to replicate the features of natural enzymes with regards to their constitutional complexity and cooperative motions, and eventually decipher the conformation-based catalytic mystery of natural enzymes.展开更多
基金supported by the National Natural Science Foundation of China(21671203 and 21877131)RGC of Hong Kong(17305415 and 17333616)+1 种基金the Ministry of Education of China(IRT-17R111)the Fundamental Research Funds for the Central Universities.
文摘Staphylococcus aureus produces staphyloxanthin,a C30 carotenoid with golden color,as an antioxidant to promote bacterial resistance to reactive oxygen species.The biosynthesis pathway of staphyloxanthin involves a series of catalytic enzymes.Aldehyde dehydrogenase(AldH)is a dehydrogenase recently identified to convert 4,4’-diaponeurosporenaldehyde into 4,4’-diaponeurosporenoic acid during staphyloxanthin biosynthesis.Here,we present the crystallographic structures of apo-and holo-forms of S.aureus AldH.The dimeric enzyme contains a unique C-terminal helix,which resembles a“gatekeeper”helix found in human membrane-bound fatty aldehyde dehydrogenase(FALDH).Particularly,the helix adopts“open”and“closed”conformations in apo-and holo-AldH,respectively,to control the access of the substrate tunnel.Mutagenesis in combination with in vitro and in vivo activity assays identifies several residues essential for S.aureus AldH substrate recognition and enzyme catalytic turnover.Our results provide insights into substrate recognition of S.aureus AldH toward polyunsaturated long-chain aldehydes at atomic resolution.
基金financial support from the National Natural Science Foundation of China(91027023,21234004,21274051,21221063,21004028)the 111 project(B06009)
文摘Enzymes are biomacromolecules responsible for the abundant chemical biotransformations that sustain life. Recently, biochemists have discovered that multiple conformations and numerous parallel paths are involved during the processes catalyzed by enzymes. It is plausible that the entire macromolecular scaffold is involved in catalysis via cooperative motions that result in incredible catalytic efficiency. Moreover, some enzymes can very strongly bind the transition state with an association constant of up to 1024 M-1, suggesting that covalent bond formation is a possible process during the conversion of the transition state in enzyme catalysis, in addition to the concatenation of noncovalent interactions. Supramolecular chemistry provides fundamental knowledge about the relationships between the dynamic structures and functions of organized molecules. By tak-ing advantage of supramolecular concepts, numerous supramolecular enzyme mimics with complex and hierarchical structures have been designed and investigated. Through the study of supramolecular enzyme models, a great deal of information to aid our understanding of the mechanism of catalysis by natural enzymes has been acquired. With the development of supramolec-ular artificial enzymes, it is possible to replicate the features of natural enzymes with regards to their constitutional complexity and cooperative motions, and eventually decipher the conformation-based catalytic mystery of natural enzymes.
