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N D Rawlings

Publications and source records attributed to N D Rawlings.

31 records · Page 2Linked to original sources
PubMed1993

Evolutionary families of peptidases.

The available amino acid sequences of peptidases have been examined, and the enzymes have been allocated to evolutionary families. Some of the families can be grouped together in 'clans' that show signs of distant relationship, but nevertheless, it appears that there may be as many as 60 evolutionary lines of peptidases with separate origins. Some of these contain members with quite diverse peptidase activities, and yet there are some striking examples of convergence. We suggest that the classification by families could be used as an extension of the current classification by catalytic type.

Amino Acid Sequence↗
PubMed1992

The baculovirus Autographa californica nuclear polyhedrosis virus genome includes a papain-like sequence.

The published DNA sequence that includes the gene for the envelope glycoprotein gp67 of the baculovirus Autographa californica nuclear polyhedrosis virus also contains a segment that shows 32% amino acid identity to papain, a cysteine endopeptidase from the papaya plant (Carica papaya). The viral papain-like sequence is apparently affected by a frame-shift mutation, but otherwise appears capable of encoding a functional enzyme. Catalytically essential amino acids appear to be conserved, as do disulphide bridges. The overall structure of the putative protein is similar to that of papain, as judged by hydropathy profile. Secondary structure prediction using a consensus of seven methods indicates that the putative viral enzyme retains the alpha/beta domain structure of papain, including the long helix beginning with cysteine-25. Infecting SF9 cells with the virus did not lead to a detected increase in cysteine endopeptidase activity, and a cysteine endopeptidase inactivator appeared to have no effect on infectivity. Irrespective of whether the sequence encodes a functionally active cysteine endopeptidase, this is the first example of a papain-related sequence in a viral genome.

Amino Acid Sequence↗
PubMed1992

Oligopeptidases, and the emergence of the prolyl oligopeptidase family.

Oligopeptidases are endopeptidases that are not proteinases in the strict sense, since they do not hydrolyse peptide bonds in proteins, but act only on smaller polypeptides or oligopeptides. These enzymes apparently perform important, specialized biological functions that include the modification or destruction of peptide messenger molecules. Oligopeptidases have few naturally occurring inhibitors, and their distinctive specificity prevents them from interacting with alpha 2-macroglobulin, unlike the great majority of endopeptidases. The specificity of these specialized endopeptidases doubtless depends upon the three-dimensional structure of the active site, but no crystallographic structure is yet available for an oligopeptidase. Study of the primary structure of prolyl oligopeptidase has recently shown that it is a member of a new family of serine-type peptidases most of which are exopeptidases. The alignment of the sequences leads to the identification of some catalytic triad residues that have not yet been elucidated experimentally.

Amino Acid Sequence↗
PubMed1991

Homologues of insulinase, a new superfamily of metalloendopeptidases.

On the basis of a statistical analysis of an alignment of the amino acid sequences, a new superfamily of metalloendopeptidases is proposed, consisting of human insulinase, Escherichia coli protease III and mitochondrial processing endopeptidases from Saccharomyces and Neurospora. These enzymes do not contain the 'HEXXH' consensus sequence found in all previously recognized zinc metalloendopeptidases.

Amino Acid Sequence↗
PubMed1990

Evolution of proteins of the cystatin superfamily.

We have examined the amino acid sequences of a number of proteins that have been suggested to be related to chicken cystatin, a protein from chicken egg white that inhibits cysteine proteinases. On the basis of statistical analysis, the following proteins were found to be members of the cystatin superfamily: human cystatin A, rat cystatin A(alpha), human cystatin B, rat cystatin B(beta), rice cystatin, human cystatin C, ox colostrum cystatin, human cystatin S, human cystatin SA, human cystatin SN, chicken cystatin, puff adder cystatin, human kininogen, ox kininogen, rat kininogen, rat T-kininogens 1 and 2, human alpha 2HS-glycoprotein, and human histidine-rich glycoprotein. Fibronectin is shown not to be a member of this superfamily, and the c-Ha-ras oncogene protein p21 (Val-12) probably is not a member also. It was convenient to divide members of the superfamily into four types on the basis of the presence of one, two, or three copies of cystatin-like segments and the presence or absence of disulfide bonds. Evolutionary dendrograms were calculated by three methods, and from these we have constructed a scheme depicting the sequence of events in the evolution of these proteins. We suggest that about 1000 million years ago a precursor containing disulfide loops appeared, and that all disulfide-containing cystatins are derived from this. We follow the evolution of the proteins of the superfamily along four main lineages, with special attention to the part that duplication of segments has played in the development of the more complex molecules.

Amino Acid Sequence↗
PubMed1989

Papaya proteinase IV amino acid sequence.

The amino acid sequence of papaya proteinase IV (PPIV), a major proteinase from the latex of Carica papaya [(1989) Biochem. J. 261, 469-476] is described. The enzyme has a high degree of sequence identity with papaya proteinase III, chymopapain and papain (81, 70 and 67%, respectively), and is clearly a member of the papain superfamily of cysteine proteinases. Nevertheless, the sequence shows substitution of certain residues conserved in all other known members of the superfamily. It is suggested that some of these substitutions may account for the unusual specificity of PPIV.

Amino Acid Sequence↗
PubMed1989

Stem bromelain: amino acid sequence and implications for weak binding of cystatin.

The amino acid sequence of stem bromelain, the major cysteine proteinase from pineapple stem is described. It shows that the enzyme is a member of the papain superfamily of cysteine proteinases, but is not very closely related to any other known member of this group. The sequence shows mutation or deletion of several residues that have been conserved in cysteine proteinases examined previously, including Asn-175 (papain). We suggest that some of these changes have the effect of altering the active-site geometry of stem bromelain, and that this accounts for the resistance of the enzyme to inhibition by cystatins and E-64[L-3-carboxy-2,3-trans-epoxypropionylleucylamido(4-guanidino)b utane].

Amino Acid Sequence↗
PubMedDate not supplied

The MEROPS database as a protease information system.

Peptidases (often termed proteases) are of great relevance to biology, medicine, and biotechnology. This practical importance creates a need for an integrated source of information about peptidases. In the MEROPS database (www.merops.ac.uk), peptidases are classified by structural similarities in the parts of the molecules responsible for their enzymatic activity. They are grouped into families on the basis of amino acid sequence homology, and the families are assembled into clans in light of evidence that they share common ancestry. The evidence for clan-level relationships usually comes from similarities in tertiary structure, but we suggest that secondary structure profiles may also be useful in the future. The classification forms a framework around which a wealth of supplementary information about the peptidases is organized. This includes images of three-dimensional structures, alignments of matching human and mouse ESTs, comments on biomedical relevance, human and other gene symbols, and literature references linked to PubMed. For each family, there is an amino acid sequence alignment and a dendrogram. There is a list of all peptidases known from each of over 1000 species, together with summary data for the distributions of the families and clans throughout the major groups of organisms. A set of online searches provides access to information about the location of peptidases on human chromosomes and peptidase substrate specificity.

Amino Acid Sequence↗