Biomaterial Database

Binding of S-methyl-5'-thioadenosine and S-adenosyl-L-methionine to protein MJ0100 triggers an open-to-closed conformational change in its CBS motif pair. 2010

María Lucas, and José Antonio Encinar, and Egoitz Astigarraga Arribas, and Iker Oyenarte, and Inmaculada Gómez García, and Danel Kortazar, and José A Fernández, and Jose M Mato, and María Luz Martínez-Chantar, and Luis Alfonso Martínez-Cruz

Unidad de Biología Estructural, CIC bioGUNE, Parque Tecnológico de Bizkaia, Ed. 800, 48160-Derio, Bizkaia, Spain.

Cystathionine beta-synthase (CBS) domains are small motifs that are present in proteins with completely different functions. Several genetic diseases in humans have been associated with mutations in their sequence, which has made them promising targets for rational drug design. The protein MJ0100 from Methanocaldococcus jannaschii includes a DUF39 domain of so far unknown function and a CBS domain pair (Bateman domain) at its C-terminus. This work presents the crystallographic analysis of four different states of the CBS motif pair of MJ0100 in complex with different numbers of S-adenosyl-L-methionine (SAM) and S-methyl-5'-thioadenosine (MTA) ligands, providing evidence that ligand-induced conformational reorganization of Bateman domain dimers could be an important regulatory mechanism. These observations are in contrast to what is known from most of the other Bateman domain structures but are supported by recent studies on the magnesium transporter MgtE. Our structures represent the first example of a CBS domain protein complexed with SAM and/or MTA and might provide a structural basis for understanding the molecular mechanisms regulated by SAM upon binding to the C-terminal domain of human CBS, whose structure remains unknown.

UI	MeSH Term	Description	Entries
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
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
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
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000241	Adenosine	A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.	Adenocard,Adenoscan
D000494	Allosteric Regulation	The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.	Regulation, Allosteric,Allosteric Regulations,Regulations, Allosteric
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D012436	S-Adenosylmethionine	Physiologic methyl radical donor involved in enzymatic transmethylation reactions and present in all living organisms. It possesses anti-inflammatory activity and has been used in treatment of chronic liver disease. (From Merck, 11th ed)	AdoMet,Ademetionine,FO-1561,Gumbaral,S Amet,S-Adenosyl-L-Methionine,S-Adenosylmethionine Sulfate Tosylate,SAM-e,Samyr,FO 1561,FO1561,S Adenosyl L Methionine,S Adenosylmethionine,S Adenosylmethionine Sulfate Tosylate
D013872	Thionucleosides	Nucleosides in which the base moiety is substituted with one or more sulfur atoms.