Invariant Thr(244) is essential for the efficient acylation step of the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans (344 views)
Biochem J (ISSN: 0264-6021, 1470-8728electronic, 0264-6021linking), 2006 Dec 15; 400: 521-530.
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Paper type: Journal Article,
Impact factor: 4.1, 5-year impact factor: 4.95
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-33845743960&partnerID=40&md5=08df48a13d4de21732b254eaf0e01ba6
Keywords: Acylation Step, Aldehyde Dehydrogenase (aldh), Hydride Transfer, Nicotinamide Conformation, Streptococcus Mutans, X-Ray Structure, Bacteria, Complexation, Hydrogen Bonds, Stereochemistry, Enzymes, Alanine, Cysteine, Glyceraldehyde 3 Phosphate Dehydrogenase, Lysine, Serine, Threonine, Bipyridine, Dithiodipyridine, -Dipyridyl Disulfide, Drug Derivative, Isoenzyme, Nicotinamide Adenine Dinucleotide Phosphate, Amino Acid Substitution, Article, Controlled Study, Crystal Structure, Enzyme Conformation, Enzyme Kinetics, Enzyme Mechanism, Enzyme Phosphorylation, Mutational Analysis, Nonhuman, Ph Measurement, Priority Journal, Steady State, Stereospecificity, Amino Acid Sequence, Binding Site, Enzymology, Genetics, Metabolism, Protein Conformation, Glyceraldehyde-3-Phosphate Dehydrogenases, Hydrogen-Ion Concentration,
Affiliations:
*** IBB - CNR ***
UMR 7567 Nancy-Université, CNRS, Faculté des Sciences, 54506 Vandoeuvre Cedex, France
Groupe Biocristallographie, UMR 7036 Nancy-Université, Faculté des Sciences, 54506 Vandoeuvre Cedex, France
Istituto di Biostrutture e Bioimmagini, CNR, 80134 Napoli, Italy
References:
Not available.
Biochem J (ISSN: 0264-6021, 1470-8728electronic, 0264-6021linking), 2006 Dec 15; 400: 521-530.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 4.1, 5-year impact factor: 4.95
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-33845743960&partnerID=40&md5=08df48a13d4de21732b254eaf0e01ba6
Keywords: Acylation Step, Aldehyde Dehydrogenase (aldh), Hydride Transfer, Nicotinamide Conformation, Streptococcus Mutans, X-Ray Structure, Bacteria, Complexation, Hydrogen Bonds, Stereochemistry, Enzymes, Alanine, Cysteine, Glyceraldehyde 3 Phosphate Dehydrogenase, Lysine, Serine, Threonine, Bipyridine, Dithiodipyridine, -Dipyridyl Disulfide, Drug Derivative, Isoenzyme, Nicotinamide Adenine Dinucleotide Phosphate, Amino Acid Substitution, Article, Controlled Study, Crystal Structure, Enzyme Conformation, Enzyme Kinetics, Enzyme Mechanism, Enzyme Phosphorylation, Mutational Analysis, Nonhuman, Ph Measurement, Priority Journal, Steady State, Stereospecificity, Amino Acid Sequence, Binding Site, Enzymology, Genetics, Metabolism, Protein Conformation, Glyceraldehyde-3-Phosphate Dehydrogenases, Hydrogen-Ion Concentration,
Affiliations:
*** IBB - CNR ***
UMR 7567 Nancy-Université, CNRS, Faculté des Sciences, 54506 Vandoeuvre Cedex, France
Groupe Biocristallographie, UMR 7036 Nancy-Université, Faculté des Sciences, 54506 Vandoeuvre Cedex, France
Istituto di Biostrutture e Bioimmagini, CNR, 80134 Napoli, Italy
References:
Not available.
Invariant Thr(244) is essential for the efficient acylation step of the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans
One of the most striking features of several X-ray structures of CoA-independent ALDHs (aldehyde dehydrogenases) in complex with NAD(P) is the conformational flexibility of the NMN moiety. However, the fact that the rate of the acylation step is high in GAPN (non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase) from Streptococcus mutans implies an optimal positioning of the nicotinamide ring relative to the hemithioacetal intermediate within the ternary GAPN complex to allow an efficient and stereospecific hydride transfer. Substitutions of serine for invariant Thr(244) and alanine for Lys(178) result in a drastic decrease of the efficiency of hydride transfer which becomes rate-limiting. The crystal structure of the binary complex T244S GAPN-NADP shows that the absence of the P-methyl group leads to a well-defined conformation of the NMN part, including the nicotinamide ring, clearly different from that depicted to be suitable for an efficient hydride transfer in the wild-type. The similar to 0.6-unit increase in pK(app) of the catalytic Cys(302) observed in the ternary complex for both mutated GAPNs is likely to be due to a slight difference in positioning of the nicotinamide ring relative to Cys(302) with respect to the wild-type ternary complex. Taken together, the data support a critical role of the Thr(244) beta-methyl group, held in position through a hydrogen-bond interaction between the Thr(244) beta-hydroxy group and the epsilon-amino group of Lys(178), in permitting the nicotinamide ring to adopt a conformation suitable for an efficient hydride transfer during the acylation step for all the members of the CoA-independent ALDH family.
One of the most striking features of several X-ray structures of CoA-independent ALDHs (aldehyde dehydrogenases) in complex with NAD(P) is the conformational flexibility of the NMN moiety. However, the fact that the rate of the acylation step is high in GAPN (non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase) from Streptococcus mutans implies an optimal positioning of the nicotinamide ring relative to the hemithioacetal intermediate within the ternary GAPN complex to allow an efficient and stereospecific hydride transfer. Substitutions of serine for invariant Thr(244) and alanine for Lys(178) result in a drastic decrease of the efficiency of hydride transfer which becomes rate-limiting. The crystal structure of the binary complex T244S GAPN-NADP shows that the absence of the P-methyl group leads to a well-defined conformation of the NMN part, including the nicotinamide ring, clearly different from that depicted to be suitable for an efficient hydride transfer in the wild-type. The similar to 0.6-unit increase in pK(app) of the catalytic Cys(302) observed in the ternary complex for both mutated GAPNs is likely to be due to a slight difference in positioning of the nicotinamide ring relative to Cys(302) with respect to the wild-type ternary complex. Taken together, the data support a critical role of the Thr(244) beta-methyl group, held in position through a hydrogen-bond interaction between the Thr(244) beta-hydroxy group and the epsilon-amino group of Lys(178), in permitting the nicotinamide ring to adopt a conformation suitable for an efficient hydride transfer during the acylation step for all the members of the CoA-independent ALDH family.
Invariant Thr(244) is essential for the efficient acylation step of the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans
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Invariant Thr(244) is essential for the efficient acylation step of the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans
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Merlino A, Russo Krauss I, Rossi B, De Vendittis A, Marco S, De Vendittis E, Vergara A, Sica F
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Pennacchio A, Giordano A, Esposito L, Langella E, Rossi M, Raia CA
* Insight into the stereospecificity of short-chain Thermus thermophilus alcohol dehydrogenase showing pro-S hydride transfer and Prelog enantioselectivity (611 views)
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D'Ambrosio K, Pailot A, Talfournier F, Didierjean C, Benedetti E, Aubry A, Branlant G, Corbier C
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Impact Factor: 3.633
View Export to BibTeX Export to EndNote
* Identification of an active dimeric intermediate populated during the unfolding process of the cambialistic superoxide dismutase from Streptococcus mutans (360 views)
Biochimie (ISSN: 0300-9084, 1638-6183, 1638-6183electronic), 2012 Mar; 94(3): 768-775.
Impact Factor: 3.142
View Export to BibTeX Export to EndNote
Pennacchio A, Giordano A, Esposito L, Langella E, Rossi M, Raia CA
* Insight into the stereospecificity of short-chain Thermus thermophilus alcohol dehydrogenase showing pro-S hydride transfer and Prelog enantioselectivity (611 views)
Protein Pept Lett (ISSN: 0929-8665, 1875-5305), 2010 Apr; 17(4): 437-443.
Impact Factor: 1.849
View Export to BibTeX Export to EndNote
D'Ambrosio K, Pailot A, Talfournier F, Didierjean C, Benedetti E, Aubry A, Branlant G, Corbier C
* The first crystal structure of a thioacylenzyme intermediate in the ALDH family: New coenzyme conformation and relevance to catalysis (423 views)
Biochemistry (ISSN: 0006-2960, 1520-4995, 1520-4995electronic), 2006 Mar 7; 45(9): 2978-2986.
Impact Factor: 3.633
View Export to BibTeX Export to EndNote
3 Records (3 excluding Abstracts).
Total impact factor: 8.624 (8.624 excluding Abstracts).
Total 5 year impact factor: 8.109 (8.109 excluding Abstracts).
Total impact factor: 8.624 (8.624 excluding Abstracts).
Total 5 year impact factor: 8.109 (8.109 excluding Abstracts).
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