Biomaterial Database

Structural studies of the role of the active site metal in metalloenzymes. 1993

H Feinberg, and H M Greenblatt, and G Shoham

Department of Inorganic Chemistry, Hebrew University of Jerusalem, Israel.

This paper describes several experimental and computational methods which are currently used in the structural analysis of metal-containing macromolecules. A specific family of proteolytic enzymes which contain a zinc cation in the active site was selected to demonstrate these methods. A range of studies using one example from this family of enzymes is described which serves to clarify the role of the metal in the overall protein structure and in the local conformation of the active site in the native enzyme, the metal-deficient enzyme, and the metal-substituted enzyme and in complexes of the enzyme with various chemical analogues. The main experimental method described is X-ray crystallography, while computational methods for the examination of surface interactions and electrostatic potential effects are described briefly to complement the structural conclusions. The various experimental and computational results are then assembled in order to draw general conclusions on the structure-function relationships of metalloproteins and in particular the role of the metal in metal-containing proteolytic enzymes. The results of these studies implicate the zinc ion in the binding and catalytic activation of the substrate and stabilization of the tetrahedral reaction intermediate. It appears that in this family of enzymes a divalent metal cation is important for the required catalytic arrangement of functional groups in the active site, especially the metal ligands. However, once an appropriate metal ion is coordinated, there is practically no effect of the particular metal ion bound on either the overall three dimensional structure of the enzyme or the local detailed structure of its active site.

UI	MeSH Term	Description	Entries
D008666	Metalloendopeptidases	ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.	Metallo-Endoproteinases,Metalloendopeptidase
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
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
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
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014961	X-Ray Diffraction	The scattering of x-rays by matter, especially crystals, with accompanying variation in intensity due to interference effects. Analysis of the crystal structure of materials is performed by passing x-rays through them and registering the diffraction image of the rays (CRYSTALLOGRAPHY, X-RAY). (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	Xray Diffraction,Diffraction, X-Ray,Diffraction, Xray,Diffractions, X-Ray,Diffractions, Xray,X Ray Diffraction,X-Ray Diffractions,Xray Diffractions
D015032	Zinc	A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.