Global conformational change associated with the two-step reaction catalyzed by Escherichia coli lipoate-protein ligase A. 2010

Kazuko Fujiwara, and Nobuo Maita, and Harumi Hosaka, and Kazuko Okamura-Ikeda, and Atsushi Nakagawa, and Hisaaki Taniguchi
Institute for Enzyme Research, University of Tokushima, Kuramotocho 3-chome, Tokushima 770-8503. Electronic address: fujiwara@ier.tokushima-u.ac.jp.

Lipoate-protein ligase A (LplA) catalyzes the attachment of lipoic acid to lipoate-dependent enzymes by a two-step reaction: first the lipoate adenylation reaction and, second, the lipoate transfer reaction. We previously determined the crystal structure of Escherichia coli LplA in its unliganded form and a binary complex with lipoic acid (Fujiwara, K., Toma, S., Okamura-Ikeda, K., Motokawa, Y., Nakagawa, A., and Taniguchi, H. (2005) J Biol. Chem. 280, 33645-33651). Here, we report two new LplA structures, LplA.lipoyl-5'-AMP and LplA.octyl-5'-AMP.apoH-protein complexes, which represent the post-lipoate adenylation intermediate state and the pre-lipoate transfer intermediate state, respectively. These structures demonstrate three large scale conformational changes upon completion of the lipoate adenylation reaction: movements of the adenylate-binding and lipoate-binding loops to maintain the lipoyl-5'-AMP reaction intermediate and rotation of the C-terminal domain by about 180 degrees . These changes are prerequisites for LplA to accommodate apoprotein for the second reaction. The Lys(133) residue plays essential roles in both lipoate adenylation and lipoate transfer reactions. Based on structural and kinetic data, we propose a reaction mechanism driven by conformational changes.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008063 Thioctic Acid An octanoic acid bridged with two sulfurs so that it is sometimes also called a pentanoic acid in some naming schemes. It is biosynthesized by cleavage of LINOLEIC ACID and is a coenzyme of oxoglutarate dehydrogenase (KETOGLUTARATE DEHYDROGENASE COMPLEX). It is used in DIETARY SUPPLEMENTS. Lipoic Acid,Alpha-Lipogamma,Alpha-Lipon Stada,Alpha-Liponsaure Sofotec,Alpha-Lippon AL,Alphaflam,Azulipont,Fenint,Juthiac,Liponsaure-ratiopharm,MTW-Alphaliponsaure,Neurium,Pleomix-Alpha,Pleomix-Alpha N,Thioctacid,Thioctacide T,Thiogamma Injekt,Thiogamma oral,Tromlipon,Verla-Lipon,alpha-Lipoic Acid,alpha-Liponaure Heumann,alpha-Liponsaure von ct,alpha-Vibolex,biomo-lipon,duralipon,espa-lipon,Acid, alpha-Lipoic,Alpha Lipogamma,Alpha Lipon Stada,Alpha Liponsaure Sofotec,Alpha Lippon AL,AlphaLipogamma,AlphaLipon Stada,AlphaLiponsaure Sofotec,AlphaLippon AL,Injekt, Thiogamma,Liponsaure ratiopharm,Liponsaureratiopharm,MTW Alphaliponsaure,MTWAlphaliponsaure,Pleomix Alpha,Pleomix Alpha N,PleomixAlpha,PleomixAlpha N,Verla Lipon,VerlaLipon,alpha Lipoic Acid,alpha Liponaure Heumann,alpha Liponsaure von ct,alpha Vibolex,alphaLiponaure Heumann,alphaLiponsaure von ct,alphaVibolex,biomo lipon,biomolipon,espa lipon,espalipon
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D010453 Peptide Synthases Ligases that catalyze the joining of adjacent AMINO ACIDS by the formation of carbon-nitrogen bonds between their carboxylic acid groups and amine groups. Peptide Synthetases,Acid-Amino-Acid Ligases,Acid Amino Acid Ligases,Ligases, Acid-Amino-Acid,Synthases, Peptide,Synthetases, Peptide
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D002384 Catalysis The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction. Catalyses
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D000249 Adenosine Monophosphate Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position. AMP,Adenylic Acid,2'-AMP,2'-Adenosine Monophosphate,2'-Adenylic Acid,5'-Adenylic Acid,Adenosine 2'-Phosphate,Adenosine 3'-Phosphate,Adenosine 5'-Phosphate,Adenosine Phosphate Dipotassium,Adenosine Phosphate Disodium,Phosphaden,2' Adenosine Monophosphate,2' Adenylic Acid,5' Adenylic Acid,5'-Phosphate, Adenosine,Acid, 2'-Adenylic,Acid, 5'-Adenylic,Adenosine 2' Phosphate,Adenosine 3' Phosphate,Adenosine 5' Phosphate,Dipotassium, Adenosine Phosphate,Disodium, Adenosine Phosphate,Monophosphate, 2'-Adenosine,Phosphate Dipotassium, Adenosine,Phosphate Disodium, Adenosine

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