The PROSITE database, its status in 1999

Hofmann, Kay; Bucher, Philip; Falquet, Laurent; Bairoch, Amos Marc

doi:10.1093/nar/27.1.215

Cited by 1,034 publications

(554 citation statements)

References 12 publications

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“…This motif used as a query finds a match with all fetuin-As and fetuinBs as well as with a few other, apparently unrelated, proteins in databanks, whereas a N-terminally extended DXLETXCHXL motif only matches with fetuin-As and fetuin-Bs (results not shown). The short LETXCHXL motif is part of the larger LETXCHXLDPTP, itself considered a fetuin signature [29], but the DPTP tetrapeptide in this signature is absent in fetuin-Bs (see above). Therefore, we now propose that the DXLETXCHXL motif represents the genuine signature of the fetuin family whereas the LETXCHXLDPTP motif should be considered as a more restricted, fetuin-A-specific signature.…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, fetuin-B did not fully retain these residues and hence a cystatin activity for this protein is most unlikely. Elsewhere, the PROSITE pattern associated with Kunitz-type inhibitors [29] is found in none of the fetuin-A or fetuin-B sequences, although fetuin-A D2 harbours an active Kunitz-type inhibitory site [21]. Therefore, we relied on another Kunitz inhibitor-associated motif that is located around the active site (Figure 4, top).…”

Section: Discussionmentioning

confidence: 99%

“…The PROSITE [29] and BLOCKS [30] databases were searched with the MOTIFS (Wisconsin package, version 8) and BLIMPS [31] programs for the occurrence of known patterns in our ORFs used as a query. Multiple alignments of DNA or Fetuin B protein sequences were done with the CLUSTALW (version 1.7) software.…”

Section: Protein-sequence Comparisonsmentioning

confidence: 99%

“…The signal peptides for fetuin-A, as proposed in [4,7], or fetuin-B, as inferred from [45], are boxed. The LETXCHXLDPTP fetuin signature [7,34] found in the PROSITE database [29] is underlined. Likewise, the 12 critical Cs used as a fetuin signature [2,34] are marked with $.…”

Section: Figure 1 Multiple Alignment Of Rat Mouse and Human Fetuin-bmentioning

confidence: 99%

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Fetuin-B, a second member of the fetuin family in mammals

Olivier

Soury

Ruminy

et al. 2000

Biochemical Journal

112

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A set of orthologous plasma proteins found in human, sheep, pig, cow and rodents, now collectively designated fetuin-A, constitutes the fetuin family. Fetuin-A has been identified as a major protein during fetal life and is also involved in important functions such as inhibition of the insulin receptor tyrosine kinase activity, protease inhibitory activities and development-associated regulation of calcium metabolism and osteogenesis. Furthermore, fetuin-A is a key partner in the recovery phase of an acute inflammatory response. We now describe a second protein of the fetuin family, called fetuin-B, which is found at least in human and rodents. On grounds of domain homology, overall conservation of cysteine residues and chromosomal assignments of the corresponding genes in these species, fetuin-B is unambiguously a paralogue of fetuin-A. Yet, fetuin-A and fetuin-B exhibit significant differences at the amino acid sequence level, notably including variations with respect to the archetypal fetuin-specific signature. Differences and similarities in terms of gene regulation were also observed. Indeed, studies performed during development in rat and mouse showed for the first time high expression of a member of the fetuin family in adulthood, as shown with the fetuin-B mRNA in rat. However, like its fetuin-A counterpart, the fetuin-B mRNA level is down-regulated during the acute phase of experimentally induced inflammation in rat.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Protein-sequence Comparisonsmentioning

confidence: 99%

Section: Figure 1 Multiple Alignment Of Rat Mouse and Human Fetuin-bmentioning

confidence: 99%

See 2 more Smart Citations

Fetuin-B, a second member of the fetuin family in mammals

Olivier

Soury

Ruminy

et al. 2000

Biochemical Journal

112

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“…deviation = 3.4 Å for 158 residues). A PAPT family signature V-(LA)-(LIV)(2)-G-G-G-X-G-X(2)-(LIV)-X-E (where X is any amino acid) has been previously defined (PROSITE entry PS01330) 11 ; this motif is located at the end of β7 and corresponds structurally to motif I in Mtases 12 . In these MTases, the catalytic residues are located in the P-loop (motif IV).…”

Section: The Papt Foldmentioning

confidence: 99%

The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor

Korolev

Ikeguchi

Skarina³

et al. 2001

Nat. Struct Biol.

134

164

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Polyamines are essential in all branches of life. Spermidine synthase (putrescine aminopropyltransferase, PAPT) catalyzes the biosynthesis of spermidine, a ubiquitous polyamine. The crystal structure of the PAPT from Thermotoga maritima (TmPAPT) has been solved to 1.5 Å resolution in the presence and absence of AdoDATO (S-adenosyl-1,8-diamino-3-thiooctane), a compound containing both substrate and product moieties. This, the first structure of an aminopropyltransferase, reveals deep cavities for binding substrate and cofactor, and a loop that envelops the active site. The AdoDATO binding site is lined with residues conserved in PAPT enzymes from bacteria to humans, suggesting a universal catalytic mechanism. Other conserved residues act sterically to provide a structural basis for polyamine specificity. The enzyme is tetrameric; each monomer consists of a C-terminal domain with a Rossmann-like fold and an Nterminal β-stranded domain. The tetramer is assembled using a novel barrel-type oligomerization motif.The nearly ubiquitous polyamines (putrescine, spermidine and spermine) are polycationic mediators of cell proliferation and differentiation 1 whose functions likely provide both stability and neutralization for nucleic acids. The abundance of polyamines is tightly regulated through biosynthesis, degradation, uptake and efflux 2 . The biosynthesis of polyamines is carried out by three highly conserved polyamine biosynthetic enzymes ( Fig. 1): ornithine decarboxylase, putrescine amino-propyltransferase (PAPT) and spermidine aminopropyltransferase (SAPT). The strong correlation of polyamine synthesis with cell growth renders these aminopropyl transferases (APTs) attractive targets for the development of antiproliferative therapeutics. The APTs are known to be inhibited by their common nucleoside product, as well as other nucleoside analogs. Most inhibitors, such as the nucleoside-polyamine adduct 4 , is also a potent inhibitor of PAPT.The catalytic mechanism of polyamine biosynthesis is unclear, partly because there is no detailed structural information for this class of enzymes. To provide structural insights into the mechanism of spermidine synthesis, the crystal structure of PAPT from Thermotoga maritima (TmPAPT) was determined at high resolution in ligand-free and AdoDATO-bound states. These structures provide insight into the function of the enzyme and its potential mechanism of action. The identification of conserved active site residues should enable accurate models of the mammalian enzymes. The PAPT foldThe structure of TmPAPT was solved using multiwavelength anomalous diffraction (MAD) from selenomethionine (SeMet)-containing crystals. The TmPAPT monomer consists of two domains: an N-terminal domain, composed of six β-strands, and a Rossmann-like C-terminal domain (Fig. 2). The larger C-terminal catalytic core domain (residues 75-296) consists of a seven-stranded β-sheet with a strand order of 9↑, 8↑, 7↑, 10↑, 11↑, 13↓, 12↑ flanked by nine α-helices. This domain resembles a topology observed in...

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Analysis of the HIV-1nef gene in five intravenous drug users with long-term nonprogressive HIV-1 infection in Italy

et al. 2000

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Great variability in the course of human immunodeficiency virus type 1 (HIV-1) infection results from a complex interplay between host and virus factors. Some of the patients with prolonged nonprogressive infection have been reported to harbor virus variants with gross deletions in the accessory nef gene that has been implicated in in vivo pathogenicity in simian and mouse models. To investigate the role of nef-deleted HIV-1 in long-term nonprogressor (LTNP) drug addicts in Italy the nef sequence from proviral DNA was analyzed from five LTNPs and five rapid progressor controls. Only small (2-12 amino acids) in-frame deletions and insertions were detected in the N-terminal polymorphic and variable regions obtained from three LTNPs and one rapid progressor. There was no evidence of premature termination of the Nef protein and all of the identified functional motifs were well conserved in both groups. Phylogenetic analysis showed interdigitation of nef sequences obtained from LTNPs and rapid progressors. The nef sequence of one LTNP, however, diverged significantly from those of the other patients. Availability of two additional blood DNA samples obtained previously from this subject allowed to detect evolution of nef at 14-17 years of HIV-1 infection, including progressive deletions. Although alterations of nef may be relatively frequent and continue to evolve in LTNPs, this study of a small number of patients does not indicate that gross deletions or loss of functional motifs play a major role in delaying or halting disease progression in infected drug abusers in Italy.

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The PROSITE database, its status in 1999

Cited by 1,034 publications

References 12 publications

Fetuin-B, a second member of the fetuin family in mammals

Fetuin-B, a second member of the fetuin family in mammals

The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor

Analysis of the HIV-1nef gene in five intravenous drug users with long-term nonprogressive HIV-1 infection in Italy

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