Biomaterial Database

Thermal stability of homologous neutral metalloendopeptidases in thermophilic and mesophilic bacteria: structural considerations. 1976

M K Pangburn, and P L Levy, and K A Walsh, and H Neurath

Thermolysin and neutral protease A are neutral metalloendopeptidases having similar specificity, molecular weight, metal content, and amino acid composition. Thermolysin, derived from the thermophilic organism Bacillus thermoproteolyticus, is heat inactivated at about 84 degrees whereas neutral protease A, derived from the mesophilic organism Bacillus subtilis, is inactivated at about 59 degrees. Structural analyses reveal that the two enzymes are homologous. Of the 326 residues of neutral protease A, 171 have been placed in sequence and 49% of these have been found in identical loci in thermolysin. These include many of the residues corresponding to the active site of thermolysin. The sensitivity of both enzymes to thermal inactivation is dependent upon the presence of calcium and neutral protease appears to bind less calcium than thermolysin. Structural data indicate that many of the ligands associated with calcium sites 1 and 2 (double site of thermolysin) are present in neutral protease and that calcium site 4 cannot exist in neutral protease. The structural homology and functional analogy of these two proteins support the concept that they have similar conformations. The known structure of thermolysin is used as a model to discuss structural differences which might be related to thermal stability.

UI	MeSH Term	Description	Entries
D008628	Mercury	A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to MERCURY POISONING. Because of its toxicity, the clinical use of mercury and mercurials is diminishing.
D008667	Metalloproteins	Proteins that have one or more tightly bound metal ions forming part of their structure. (Dorland, 28th ed)	Metalloprotein
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D010447	Peptide Hydrolases	Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.	Peptidase,Peptidases,Peptide Hydrolase,Protease,Proteases,Proteinase,Proteinases,Proteolytic Enzyme,Proteolytic Enzymes,Esteroproteases,Enzyme, Proteolytic,Hydrolase, 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
D011489	Protein Denaturation	Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.	Denaturation, Protein,Denaturations, Protein,Protein Denaturations
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D005561	Formates	Derivatives of formic acids. Included under this heading are a broad variety of acid forms, salts, esters, and amides that are formed with a single carbon carboxy group.	Formic Acids,Acids, Formic
D006358	Hot Temperature	Presence of warmth or heat or a temperature notably higher than an accustomed norm.	Heat,Hot Temperatures,Temperature, Hot,Temperatures, Hot
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