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At least 163 records · Page 9Linked to original sources
PubMed1997

Posttranslational modification of oat phytochrome A: phosphorylation of a specific serine in a multiple serine cluster.

Phytochrome A (phyA) is a photoreceptor of higher plants which mediates a variety of biochemical and physiological processes in response to red/far-red light. By detailed structural analysis of the peptides of the total tryptic digest of oat phyA, we found that the photoreceptor isolated from red light irradiated seedlings contains only one site of phosphate attachment, in the N-terminal Ser-rich region. The N-terminal tryptic phosphopeptide (residues 1-12) contains eight serine residues, any of which may be phosphorylated. Direct fast atom bombardment mass spectrometry (FAB MS/MS) analysis of the phosphorylated peptide as well as of its phosphate-containing fragment (residues 1-9) was not successful due to their hydrophilic nature and instability of the phosphate bond. beta-Elimination of the phosphorylated tryptic peptide in the presence of ethanethiol converted the phosphoserine residue to S-ethylcysteine that is stable under FAB MS/MS. FAB MS/MS analysis of the modified peptide clearly showed that the phosphate group was attached to Ser7. The in vivo phosphorylation site at Ser7 in oat phyA is discussed for its possible regulatory role in phyA function.

Amino Acid Sequence↗
PubMed1975

Tertiary structural differences between microbial serine proteases and pancreatic serine enzymes.

Although primary structural homology between bacterial serine proteases and those from the mammalian pancreas is slight, two-thirds of the residues in the bacterial enzyme SGPB as seen at 2.8-A resolution, adopt a similar polypeptide chain conformation to that of the chymotrypsin family. The three major regions of difference show how this family of proteolytic enzymes has developed from the more primitive bacterial to the relatively sophisticated pancreatic enzymes.

Amino Acid Sequence↗
PubMed1997

Phosphorylation of human keratin 8 in vivo at conserved head domain serine 23 and at epidermal growth factor-stimulated tail domain serine 431.

Dynamic phosphorylation is one mechanism that regulates the more than 20 keratin type I and II intermediate filament proteins in epithelial cells. The major type II keratin in "simple type" glandular epithelia is keratin 8 (K8). We used biochemical and mutational approaches to localize two major in vivo phosphorylation sites of human K8 to the head (Ser-23) and tail (Ser-431) domains. Since Ser-23 of K8 is highly conserved among all type II keratins, we also examined if the corresponding Ser-59 in stratified epithelial keratin 6e is phosphorylated. Mutation of K6e Ser-59 abolished its phosphorylation in 32PO4-labeled baby hamster kidney cell transfectants. With regard to K8 phosphorylation at Ser-431, it increases dramatically upon stimulation of cells with epidermal growth factor (EGF) or after mitotic arrest and is the major K8 phosphorylated residue after incubating K8 immunoprecipitates with mitogen-activated protein or cdc2 kinases. A monoclonal antibody that specifically recognizes phosphoserine 431-K8 manifests increased reactivity with K8 and recognizes reorganized K8/18 filaments after EGF stimulation. Our results suggest that in vivo serine phosphorylation of K8 and K6e within the conserved head domain motif is likely to reflect a conserved phosphorylation site of most if not all type II keratins. Furthermore, K8 Ser-431 phosphorylation occurs after EGF stimulation and during mitotic arrest and is likely to be mediated by mitogen-activated protein and cdc2 kinases, respectively.

Animals↗
PubMed2004

Role of serine 10 phosphorylation in p27 stabilization revealed by analysis of p27 knock-in mice harboring a serine 10 mutation.

The inhibition of cyclin-dependent kinase activity by p27 contributes to regulation of cell cycle progression. Serine 10 is the major phosphorylation site of p27, and its phosphorylation has been shown to affect the stability and nuclear export of p27 at the G0-G1 transition in transfected cultured cells. To investigate the physiological relevance of p27 phosphorylation on Ser10, we generated p27 "knock-in" mice that harbor an S10A mutation in this protein. Mice homozygous for the mutation (p27(S10A/S10A) mice) were normal in body size, but the abundance of p27 was decreased in many organs, including brain, thymus, spleen, and testis. The stability of p27 in G0 phase was markedly reduced in lymphocytes of p27(S10A/S10A) mice compared with that in wild-type cells, whereas p27 stability in S phase was similar in cells of the two genotypes. The degradation of p27 in cells of the mutant mice at G0 phase was prevented by a proteasome inhibitor. These data indicate that the physiological role of p27 phosphorylation on Ser10 is to stabilize the protein in G0 phase. Unexpectedly, the nuclear export of p27 at the G0-G1 transition occurred normally in p27(S10A/S10A) mouse embryonic fibroblasts, indicating that phosphorylation of Ser10 is dispensable for this process.

Active Transport, Cell Nucleus↗
PubMed2002

A CLN2-related and thermostable serine-carboxyl proteinase, kumamolysin: cloning, expression, and identification of catalytic serine residue.

The gene encoding kumamolysin, a thermostable pepstatin-insensitive carboxyl proteinase, was cloned and expressed. (i) Kumamolysin was synthesized as a large precursor consisting of two regions: amino-terminal prepro (188 amino acids) and mature proteins (384 amino acids). (ii) The deduced amino acid sequence of the mature region exhibited high similarity to those of such bacterial pepstatin-insensitive enzymes as Pseudomonas carboxyl proteinase (PSCP; EC 3.4.23.37, identity = 37%), Xanthomonas carboxyl proteinase (XCP; EC 3.4.23.33, identity = 36%), and human CLN2 gene product (identity = 36%), which is related to a fatal neurodegenerative disease. (iii) The presumed catalytic triad, Glu78, Asp82, Ser278 [three-dimensional structure of PSCP: Wlodawer, A. et al. (2001) Nature Struct. Biol., 8, 442-446], was found to be conserved in the amino acid sequence of kumamolysin. (iv) Kumamolysin was inactivated by such aldehyde-type inhibitors as Ac-Ile-Pro-Phe-CHO (K(i) = 0.7 0.14 microM). In PSCP, it has been clarified that these inhibitors form a hemiacetal linkage with the catalytic serine residue and inactivate the enzyme. (v) Mutational analysis of the Ser278 residue revealed that the mutant lost both auto-processing activity and proteolytic activity. These results strongly suggest that kumamolysin has a unique catalytic triad consisting of Glu78, Asp82, and Ser278 residues, as previously observed for PSCP.

Amino Acid Sequence↗
PubMed2001

Description of staphylococcus serine protease (ssp) operon in Staphylococcus aureus and nonpolar inactivation of sspA-encoded serine protease.

Signature tagged mutagenesis has recently revealed that the Ssp serine protease (V8 protease) contributes to in vivo growth and survival of Staphylococcus aureus in different infection models, and our previous work indicated that Ssp could play a role in controlling microbial adhesion. In this study, we describe an operon structure within the ssp locus of S. aureus RN6390. The ssp gene encoding V8 protease is designated as sspA, and is followed by sspB, which encodes a 40.6-kDa cysteine protease, and sspC, which encodes a 12.9-kDa protein of unknown function. S. aureus SP6391 is an isogenic derivative of RN6390, in which specific loss of SspA function was achieved through a nonpolar allelic replacement mutation. In addition to losing SspA, the culture supernatant of SP6391 showed a loss of 22- to 23-kDa proteins and the appearance of a 40-kDa protein corresponding to SspB. Although the 40-kDa SspB protein could degrade denatured collagen, our data establish that this is a precursor form which is normally processed by SspA to form a mature cysteine protease. Culture supernatant of SP6391 also showed a new 42-kDa glucosaminidase and enhanced glucosaminidase activity in the 29 to 32 kDa range. Although nonpolar inactivation of sspA exerted a pleiotropic effect, S. aureus SP6391 exhibited enhanced virulence in a tissue abscess infection model relative to RN6390. Therefore, we conclude that SspA is required for maturation of SspB and plays a role in controlling autolytic activity but does not by itself exert a significant contribution to the development of tissue abscess infections.

Adhesins, Bacterial↗
PubMed2006

Phosphorylation of the menin tumor suppressor protein on serine 543 and serine 583.

Multiple endocrine neoplasia type 1 (MEN-1) is a heritable syndrome typified by tumors in multiple endocrine organs, including the pituitary, parathyroids, and pancreatic islets. MEN-1 is attributable to mutations in the MEN1 tumor-suppressor gene that encodes the menin protein. Recent studies have implicated menin in transcriptional regulation and in covalent histone modification; however, little is known about modifications of the menin protein. Here, we report that menin is subject to phosphorylation on serine residues, including Ser543 and Ser583. Phosphorylation-defective mutants of either or both of these residues retain the associated histone methyltransferase activity of menin, as well as binding to the trithorax complex members Ash2L, Rbbp5, and MLL2 and to RNA polymerase II. Chromatin immunoprecipitation experiments reveal that binding of menin to the Hoxc8 locus is not affected by phosphorylation on Ser543 or Ser583.

Cell Differentiation↗
PubMed2002

The role of serine proteases and serine protease inhibitors in the migration of gonadotropin-releasing hormone neurons.

BACKGROUND: Mechanisms regulating neuronal migration during development remain largely undefined. Extracellular matrix cues, target site released factors, and components of the migratory neurons themselves are likely all coordinated in time and space directing neurons to their appropriate locations. We have studied the effects of proteases and their inhibitors on the extracellular matrix and the consequences to the migration of gonadotropin releasing hormone (GnRH) neurons in the embryonic chick. Chick GnRH neurons differentiate in the olfactory epithelium, migrate along the olfactory nerve and enter the forebrain. The accessibility of this coherent cell group make it amenable for studying protease/inhibitor roles in migratory processes. RESULTS: Affigel blue beads were used to deliver a serine protease inhibitor, protease nexin-1 (PN-1), and a target protease, trypsin, to the olfactory epithelium coincident with initiation of GnRH neuronal migration. PN-1 inhibited neuronal migration while trypsin accelerated their transit into the CNS. Prior to initiation of migration, neither PN-1 nor trypsin altered the timing of neuronal exit. Trypsin did, however, accelerate the timing of neuronal crossing into the nerve-forebrain junction. CONCLUSIONS: These data support the hypothesis that protease activity modulates neuronal movements across barriers. Moreover, the data suggest, for the first time, that aspects of GnRH neuronal migration may be cell autonomous but modulated by ECM alterations.

Amyloid beta-Protein Precursor↗
PubMed1988

[Synthesis of N-alpha-(arylsulfonyl)-4-amidino-phenylalanyl-prolines and N-alpha-(arylsulfonylglycyl)-4-amidino-phenylalanyl-prolines and testing of them as inhibitors of serine proteinases. 33. Synthetic inhibitors of serine proteinases].

The headline compounds were prepared by the reaction of N alpha-(arylsulfonyl)- and N alpha-(arylsulfonylglycyl)-4-cyanophenylalanines to the L- and D-proline derivatives. These compounds were transformed in a usual manner in the amidino compounds. The substitution of the pyrrolidine residue by L-proline in this type of inhibitors decreased the activity against serine proteases, especially against thrombin. In the case of the D-proline derivatives the decrease of the inhibitor activity against thrombin was very high.

Chemical Phenomena↗
PubMed1990

Structure of wheat serine carboxypeptidase II at 3.5-A resolution. A new class of serine proteinase.

The structure of serine carboxypeptidase II from wheat bran has been determined to 3.5-A resolution by multiple isomorphous replacement, solvent flattening, and crystallographic refinement. The amino acid sequence has been fit to the electron density map and the model refined to a conventional crystallographic R factor of 20.9%. The molecule is an alpha + beta protein and contains a "catalytic triad" (Asp338, His397, and Ser146) similar in arrangement to those in chymotrypsin and subtilisin. The -fold of the polypeptide backbone is, however, completely different from those enzymes. This suggests that this is a third example of convergent evolution to a common enzymatic mechanism. The -fold is, on the other hand, surprisingly similar to that of the zinc proteinase carboxypeptidase A.

Amino Acid Sequence↗
PubMed1999

The absolute configuration of belactin A, a beta-lactone-containing serine carboxypeptidase inhibitor: importance of the beta-lactone structure for serine carboxypeptidase inhibition.

The absolute configuration of belactin A, a beta-lactone-containing serine carboxypeptidase inhibitor was studied by a crystal X-ray diffraction analysis and its absolute structure was determined to be (2R,3S)-2-¿(3S)-3-[(2-amino-5-chlorophenyl)carboxamido]-1,1-dimethyl-2-o xobutyl¿-3-methyl-4-oxooxetane. The importance of the beta-lactone structure for inhibitory activity was found by preparing several derivatives of belactin A.

Benzamides↗
PubMed1999

Inhibition of mutant p53 phosphorylation at serine 15 or serine 315 partially restores the function of wild-type p53.

The tumor suppressor protein p53 is a phosphoprotein and has growth and transformation suppression functions. Phosphorylation of wild-type p53 is known to modulate its function. To investigate the role of phosphorylation in modulating the functions of mutant p53, we constructed a series of phosphorylation site mutants based on mutant p53 Ala143 (p53-143) and p53 His175 (p53-175). When transfected into p53-negative Saos-2 cells, parental mutant p53-143 and p53-175 abolished both growth suppression and induction of apoptosis. However, DNA-activated protein kinase (DNA-PK) or cyclin-dependent kinase (cdks) phosphorylation site double mutants partially restored the growth suppression and induction of apoptosis and recovered the p53-specific DNA binding activity. We also observed a difference in sensitivity to calpain from parental mutants p53-175 and p53-175/15 or p53-175/315. These results suggest that the lack of phosphorylation at either the DNA-PK or cdks site in p53 mutants partially restores the wild-type functions by altering their conformation.

Apoptosis↗