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Biomedical subjects

P Ghosh

Publications and source records attributed to P Ghosh.

At least 91 records · Page 5Linked to original sources
PubMed2000

Production of tissue inhibitor of metalloproteinases 3 is selectively enhanced by calcium pentosan polysulfate in human rheumatoid synovial fibroblasts.

OBJECTIVE: To determine the effects of calcium pentosan polysulfate (CaPPS) on the production of matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMP), in cultures of rheumatoid synovial fibroblasts. METHODS: The production of MMP-1, -2, -3, -7, -8, -9, and -13 and of TIMP-1, -2, -3, and -4 in cultured rheumatoid synovial fibroblasts treated with 0.1, 1, and 10 microg/ml CaPPS in the presence and absence of 100 units/ml interleukin-1alpha (IL-1alpha) was examined by a sandwich enzyme immunoassay system and/or immunoblotting. The messenger RNA (mRNA) expression of TIMP-3 and membrane type 1 MMP was determined by Northern blotting, and the cells expressing TIMP-3 gene in rheumatoid synovium were identified by in situ hybridization. The synthesis and secretion of TIMP-3 protein were monitored by pulse-chase experiments. TIMP-3 was immunolocalized in untreated or CaPPS-treated rheumatoid synovial fibroblasts and synovium using an avidin-biotin-peroxidase complex method. RESULTS: Treatment of cultured rheumatoid synovial fibroblasts with CaPPS resulted in a dose-dependent increase in the production of TIMP-3 in both cell lysates and media from the treated cells. However, CaPPS did not affect the levels of the other MMPs or TIMPs examined. The production of TIMP-3 was further enhanced in the cells treated with both IL-1alpha and CaPPS. Immunohistochemistry confirmed the enhanced production of TIMP-3 by cells exposed to CaPPS. The mRNA level of TIMP-3 increased 3.4-fold by treating rheumatoid synovial fibroblasts with IL-1alpha, but CaPPS itself did not alter the expression levels in the IL-1alpha-treated or -untreated cells. Pulse-chase studies demonstrated that translation for TIMP-3 protein was enhanced by CaPPS treatment. In situ hybridization and immunohistochemistry indicated that TIMP-3 was expressed mainly in the hyperplastic lining cells of rheumatoid synovium, and that the production of this protein by these immunoreactive lining cells was significantly increased by treatment with CaPPS. CONCLUSION: The present study is the first to demonstrate that the new antiarthritic drug, CaPPS, selectively enhanced TIMP-3 production at the posttranscription level in cultured rheumatoid synovial fibroblasts and in the lining cells of rheumatoid synovium. By this mechanism, CaPPS may be able to modulate joint tissue destruction in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2000

Immunolocalisation of BPTI-like serine proteinase inhibitory proteins in mast cells, chondrocytes and intervertebral disc fibrochondrocytes of ovine and bovine connective tissues. An immunohistochemical and biochemical study.

A polyclonal anti-bovine pancreatic trypsin inhibitor (BPTI) IgY was raised in chickens immunised with aprotinin. The anti-BPTI IgY was subsequently isolated from egg yolks and purified to homogeneity by affinity chromatography on immobilised aprotinin and by Superose 6 size exclusion fast protein liquid chromatography (FPLC). Immunoblotting with the chicken IgY demonstrated its specificity for BPTI; 3.9 ng BPTI could be detected by this technique. There was no crossreactivity against alpha1-proteinase inhibitor (human and sheep), inter-alpha-trypsin inhibitor (human and sheep), secretory leucocyte proteinase inhibitor or a range of serine proteinase inhibitory proteins (SPIs) isolated from plant sources (soybean and lima bean trypsin inhibitor, potato trypsin and chymotrypsin inhibitors) or serum SPIs (antithrombin-III, alpha2-macroglobulin). Immunoblotting using the anti-BPTI IgY identified the 6- to 12- and 58-kDa forms of endogenous ovine cartilage SPIs in cartilage extracts, confirming the interrelationship of the ovine cartilage SPIs with BPTI. BPTI-domain SPIs were immunolocalised within mast cells of ovine and bovine duodenum, lung and pancreas, and in ovine and bovine bronchial cartilage chondrocytes, chondrocytes of the superficial and intermediate zones of articular cartilage and in the fibrochondrocytes/chondrocytes of the nucleus

Animals↗
PubMed2000

Differential expression of proteoglycan epitopes by ovine intervertebral disc cells.

The alginate bead culture system has been utilised by several groups to examine the in vitro proteoglycan (PG) metabolism of chondrocytes and intervertebral disc cells, but the nature of the PGs produced has not been examined in detail. This is largely due to the difficulty of separating the anionically charged sodium alginate support matrix from PGs which are similarly charged. In the present study ovine annulus fibrosus, transitional zone and nucleus pulposus cells were dissociated enzymatically from their respective matrices by sequential digestion with pronase/clostridial collagenase and DNAase and then cultured in alginate beads for 10 d. The beads were solubilised and subjected to DEAE Sepharose CL6B anion exchange chromatography to separate the sodium alginate bead support matrix material quantitatively from the disc cell PGs. The alginate free bead PGs were then subjected to composite agarose polyacrylamide gel electrophoresis to resolve PG populations and the PGs were transferred to nitrocellulose membranes by semidry electroblotting. The PGs were identified by probing the blots with a panel of antibodies to defined PG core protein and glycosaminoglycan side chain epitopes. Alginate beads of disc cells were also embedded in paraffin wax and 4 microm sections cut to immunolocalise decorin, biglycan, versican, and the 7-D-4 PG epitope within the beads. Decorin and biglycan had similar distributions in the beads, being localised on the cell surface whereas versican and the 7-D-4 PG epitope were immunolocalised interterritoriarly. This study is the first to demonstrate that ovine disc cells synthesise versican in alginate bead culture. Furthermore the immunoblotting studies also showed that a proportion of the 7-D-4 PG epitope was colocalised with versican.

Alginates↗
PubMed2000

Modification of articular cartilage and subchondral bone pathology in an ovine meniscectomy model of osteoarthritis by avocado and soya unsaponifiables (ASU).

OBJECTIVE: To examine the effect of an oral preparation of avocado and soya unsaponifiables (ASU) on the development of joint pathology in an ovine model of osteoarthritis (OA), using computer-assisted histomorphometric methods. DESIGN: OA was induced in ovine knee joints by bilateral lateral meniscectomy (N=32). ASU (900 mg/weekday) was given orally to half the group (MenX+ASU), the remainder receiving placebo (MenX). Sixteen animals were used as non-operated controls (NOC). At 3 and 6 months post-meniscectomy, histological sections from the medial and lateral femoral condyles (MFC, LFC), tibial plateaux (MTP, LTP) and trochlear groove (TG) were prepared from all joints. Sections were scored using traditional histopathological scales, and computerized image analysis, measuring total cartilage area, uncalcified cartilage (UCC) and subchondral bone plate (SCP) thickness, and intensity of articular cartilage toluidine blue staining (mean greyscale intensity, black=255) as an index of proteoglycan (PG) content. RESULTS: Computerized image analysis showed significant histological differences not detectable by traditional scoring methods. ASU-treated animals at 6 months showed reduced loss of toluidine blue stain in the MTP (P=0.015) and LTP (P=0.001), and significantly greater staining in the TG than either placebo or NOC groups (P=0.011). UCC thickness increased after meniscectomy, but tended to be highest in ASU-treated animals, significantly so in the middle zone of the LFC (MenX+ASU: 1.03+/-0.21mm vs MenX: 0.79+/-0.14 mm, P=0.018; NOC: 0.77+/-0.17 mm). Lateral compartment SCP thickness increased post-meniscectomy but was increased significantly less in the inner zone of the LTP in ASU-treated sheep (MenX+ASU: 1.37+/-0. 23 mm vs MenX: 1.68+/-0.28 mm, P=0.033; NOC=1.22+/-0.33 mm). CONCLUSIONS: In this model ASU treatment following meniscectomy appeared to confer a subtle but statistically significant protective effect on articular cartilage. Although the drug failed to prevent focal cartilage lesions, characteristic of this model, histomorphometric analysis demonstrated greater PG content and UCC thickness in adjacent joint regions of ASU-treated animals. In addition, a statistically significant reduction of subchondral bone sclerosis was noted in the LTP region of the drug-treated group. An anabolic effect on chondrocytes, resulting in the stimulation of matrix production in regions distant to the insult, was also suggested by the data. These findings support other studies which have proposed that ASU may exhibit disease-modifying anti-OA activity.

Animals↗
PubMed2000

Effects of chronic alcohol treatment on the synthesis, sialylation, and disposition of nascent apolipoprotein E by peritoneal macrophages of rats.

BACKGROUND: Plasma apolipoprotein (apo) E, a sialoprotein, plays an important role in reverse cholesterol transport. Previously, we showed that chronic alcohol consumption impairs glycosylation of apo E in rat liver. Peritoneal macrophages are another significant apo E synthesis site. OBJECTIVE: The main purpose of this study was to determine the effects of chronic alcohol feeding of rats on the synthesis, sialylation, and sialic acid content of macrophage apo E and its ability to bind to the HDL(3) molecule in vitro. DESIGN: Rats were fed an alcoholic diet or an isoenergetic control diet for 8 wk, after which peritoneal macrophages isolated from them were cultured and analyzed for apo E metabolism. RESULTS: Macrophages from alcohol-fed rats accumulated 33.3% more (P < 0.05) cholesterol than did those from control rats when incubated with acetylated LDL. These macrophages showed a 51-57% lower relative sialylation rate of apo E (P < 0.001) but no significant difference in relative protein synthetic rate. The sialic acid content of the intracellular and secreted forms of apo E was reduced by 41.8% (P < 0.001) and 50.3% (P < 0.001), respectively, with chronic alcohol treatment. Secretion of newly synthesized apo E was impaired by 53.7% (P < 0.001) and 26. 1% (P < 0.001) in the absence and presence of HDL in the medium, respectively. Macrophages of alcohol-treated rats secreted apo E with 47.6-67.2% lower (P < 0.001) HDL(3) binding ability; binding ability was restored completely by resialylation of the desialylated apo E. CONCLUSION: In rats, an alcohol-mediated decrease in sialylation rate resulting in loss of sialic acid residues in apo E impairs the ability of apo E to bind to HDL and consequently in defective reverse cholesterol transport.

Animals↗
PubMed2000

Apoptosis-inducing vanadocene compounds against human testicular cancer.

We systematically assessed the cytotoxic effects of five metallocene dichlorides containing vanadium (vanadocene dichloride), titanium (titanocene dichloride), zirconium (zircodocene dichloride), molybdenum (molybdocene dichloride), and hafnium (hafnocene dichloride) as the central metal atom and 19 other vanadocene complexes. These compounds were tested against the human testicular cancer cell lines Tera-2 and Ntera-2 using both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and apoptosis assays. Notably, only the vanadium(IV)-containing metallocenes exhibited significant cytotoxicity against Tera-2 and Ntera-2 cells and induced apoptosis within 24 h. Vanadocenes with dithiocyanate [VCp2(SCN)2 x 0.5 H2O] and diselenocyanate [VCp2(NCSe)2] as ancillary ligands were identified as the most potent cytotoxic compounds. Vanadocenes, especially the lead compound VCp2(NCSe)2, may be useful in the treatment of testicular cancer.

Apoptosis↗
PubMed2000

A fraction isolated from Ehrlich ascites carcinoma as an antitumor and differentiating agent against human leukemic cell ML-2.

Lipopolysaccharide fraction isolated from Ehrlich ascites carcinoma (E-LPS) was investigated as an antitumor agent against human leukemia cell ML-2. Marked cell growth inhibition was observed with ML-2 cell accompanied by inhibition of DNA synthesis and perturbation of cell cycle. Induction of differentiation in treated ML-2 cells was observed as indicated by morphological maturation, NBT reducing activity and indirect immunofluorescence.

Animals↗
PubMed1999

Amino acid substitution in alpha-helix 7 of Cry1Ac delta-endotoxin of Bacillus thuringiensis leads to enhanced toxicity to Helicoverpa armigera Hubner.

Insecticidal proteins or delta-endotoxins of Bacillus thuringiensis are highly toxic to a wide range of agronomically important pests. The toxins are formed of three structural domains. The N-terminal domain is a bundle of eight alpha-helices and is implicated in pore formation in insect midgut epithelial membranes. All the delta-endotoxins share a common hydrophobic motif of eight amino acids in alpha-helix 7. A similar motif is also present in fragment B of diphtheria toxin (DT). Site-directed mutagenesis of Cry1Ac delta-endotoxin of B. thuringiensis was carried out to substitute its hydrophobic motif with that of DT fragment B. The mutant toxin was shown to be more toxic to the larvae of Helicoverpa armigera (cotton bollworm) than the wild-type toxin. Voltage clamp analysis with planar lipid bilayers revealed that the mutant toxin opens larger ion channels and induces higher levels of conductance than the wild-type toxin.

Amino Acid Substitution↗
PubMed1999

Structural and functional characterization of seven spermicidal vanadium(IV) complexes: potentiation of activity by methyl substitution on the cyclopentadienyl rings.

In a systematic effort to identify and develop effective vanadocene(IV) complexes as a new class of contraceptive agents, the effect of methyl substitution in the cyclopentadienyl rings of Cpx2VCl2 on their spermicidal activity has been examined. The spermicidal activities of compounds Cpx2VCl2 [Cpx = Me5Cp (Cp*) (1), Cp (3), MeCp (Cp') (5)], as well as two of their corresponding vanadium(V) oxidation products Cp*V(O)Cl2 (2) and CpV(O)Cl2 (4), were examined by computer-assisted sperm analysis (CASA). These analyses have established that penta-substitution of the Cp ring by electron-donating methyl groups augments the spermicidal activity 10-fold. The corresponding V(V) oxo compounds, Cp*V(O)Cl2 (2) and CpV(O)Cl2 (4), tested under identical conditions did not show as effective spermicidal activity even though these complexes have a pseudo-tetrahedral geometry similar to the active vanadocene(IV) dichlorides. Two pseudo-octahedral V(IV) complexes with tris-pyrazolyl borate as ligand, (HBpz3)V(O)Cl.DMF (6) and (HB(3,5-Me2pz)3)V(O)Cl.DMF (7), were also found to exhibit potent spermicidal activity. Although some vanadium(IV) complexes may immobilize sperm due to the generation of .OH radicals, the lack of spermicidal activity of VOSO4 which generates .OH radicals, and the potent spermicidal activity of [Cp2V(acac)][O3SCF3] (8), and [Cp2V(DeDtc)][O3SCF3] (9) which do not generate .OH radicals, indicate that .OH radical mediated reactions may not be essential for the spermicidal activity of vanadium(IV) complexes.

Electron Spin Resonance Spectroscopy↗
PubMed1999

Molecular genotoxicity profiles of apoptosis-inducing vanadocene complexes.

Metallocene complexes containing vanadium induce apoptosis in human cancer cells by an as yet unknown mechanism and may therefore be useful as a new class of cytotoxic anticancer drugs. Ultrastructural studies showing the formation of metallocene-DNA complexes prompted the hypothesis that their mechanism of action may resemble the DNA damage induced by cisplatin. Molecular genotoxicity testing provides insights into the mechanisms of action of new chemotherapeutic agents. Therefore, we determined the effects of three cytotoxic vanadocene complexes, vanadocene dichloride, vanadocene dithiocyanate, and vanadocene dioxycyanate, on genomic stability using the yeast DEL recombination assay and transcriptional activation of genotoxic stress-specific promoters in human HepG2 cells using the CAT-Tox(L) assay. Cisplatin caused an 11-fold increase of recombination frequency in yeast and induced transcriptional activation of the DNA damage-associated promoters such as the minimum promoter containing p53 response elements and the GADD45 promoter in addition to activating the promoters for c-fos, heat shock protein 70, metallothionine IIa, and the minimum promoter containing nuclear factor kappa(kappa)B response elements. In contrast to cisplatin, vanadocene complexes did not increase the DEL recombination frequency in yeast nor did they activate any of the DNA damage-associated promoters in HepG2 cells. Vanadocene complexes triggered activation of the c-fos promoter without affecting the minimum promoter containing p53 response elements or the GADD45 promoter. These results indicate that the apoptotic signal of vanadocene complexes is not triggered by primary DNA damage and it does not require p53 induction, thereby disproving the hypothesis that it mechanistically resembles the cytotoxic action of cisplatin.

Antineoplastic Agents↗
PubMed1999

Divergent effects of dithiocarbamates on AP-1-containing and AP-1-less NFAT sites.

Changes in the redox status of cells affect NF-kappaB and activator protein (AP)-1 nuclear expression and activity. In particular, antioxidants decrease NF-kappaB and increase AP-1 transcriptional activity, thereby regulating gene expression. In T cells, low concentrations of antioxidants enhance IL-2 and inhibit IL-4 expression. Since NFAT binding sites play an essential role in regulating IL-2 and IL-4 gene transcription, we studied the effects of dithiocarbamates, using the pyrrolidine derivative of dithiocarbamate (PDTC), on the activity of the distinct AP-1-containing IL-2 NFAT and AP-1-less IL-4 NFAT enhancers elements. Consistent with the presence of AP-1 proteins within the IL-2 NFAT complex, PDTC strongly enhanced phorbol 12-myristate 13-acetate/phytohemagglutinin-induced NFAT binding to the IL-2 NFAT enhancer and transcriptional activity of a reporter plasmid driven by this NFAT enhancer. In contrast, the activity of the IL-4 NFp enhancer, which does not bind AP-1, was abolished by PDTC treatment. In the Jurkat T cell line treated with PDTC, co-expression of the Ca2+/calmodulin-dependent phosphatase, calcineurin, completely restored the IL-4 NFp enhancer activity. Our data indicate that calcineurin-mediated NFAT activity is a target for antioxidants and provides new insights into the molecular mechanisms controlling differential cytokine gene expression.

Antioxidants↗
PubMed1999

Cardiac operations in patients with low-grade small lymphocytic malignancies.

BACKGROUND: Low-grade small lymphocytic (B cell) malignancies (encompassing chronic lymphocytic leukemia and some types of non-Hodgkin lymphoma) are diseases of the elderly. Open cardiac procedures are known to have increased risk of postoperative infection and other morbidities in these immunodeficient patients. Outcome of open cardiac procedures in these patients was reviewed retrospectively. PATIENTS: Thirteen patients (aged 58-82 years, 11 men, 2 women) with these lymphocytopathologic diseases (8 with chronic lymphocytic leukemia and 5 with non-Hodgkin lymphoma) underwent cardiac operations between January 1977 and June 1998. Mean age was 72 +/- 2.1 years. Isolated coronary artery bypass grafting was performed in 11 and combined procedures and double valve replacement were performed in 1 each. Preoperatively, 9 patients were in a low-risk clinical stage. Mean preoperative duration of lymphocytopathologic disease was 6.1 +/- 1.6 years. Mean preoperative New York Heart Association functional class was 2.8. RESULTS: There was no operative death. Average stay in the intensive care unit was 41.4 +/- 8.6 hours. Postoperative leg and superficial sternal wound infections were encountered in 3 patients. Average postoperative hospital stay was 10.0 +/- 1.7 days. During the follow-up up to 72 months, 1 patient underwent a second cardiac operation. There was 1 late death 4 years later. Coronary stenting was done in 1 patient and a cardioverter-defibrillator was implanted in another patient for recurrent angina. Three patients underwent chemotherapy. Cardiac and lymphocytopathologic status remained stable in others. CONCLUSIONS: Acceptable outcome may be anticipated after cardiac operations in patients with low-grade chronic lymphocytic leukemia and non-Hodgkin lymphoma in early stages. However, the possibility of infection and progression of cardiac and lymphocytopathologic status in these patients should call for caution.

Age Factors↗
PubMed1999

The pathobiology of osteoarthritis and the rationale for the use of pentosan polysulfate for its treatment.

OBJECTIVES: Structure-modifying osteoarthritis (OA) drugs (SMOADs) may be defined as agents that reverse, retard, or stabilize the underlying pathology of OA, thereby providing symptomatic relief in the long-term. The objective of this review was to evaluate the literature on sodium pentosan polysulfate (NaPPS) and calcium pentosan polysulfate (CaPPS), with respect to the pathobiology of OA to ascertain whether these agents should be classified as SMOADs. METHODS: Published studies on NaPPS and CaPPS were selected on the basis of their relevance to the known pathobiology of OA, which also was reviewed. RESULTS: Both NaPPS and CaPPS exhibit a wide range of pharmacological activities. Of significance was the ability of these agents to support chondrocyte anabolic activities and attenuate catabolic events responsible for loss of components of the cartilage extracellular matrix in OA joints. Although some of the anti-catabolic activities may be mediated through direct enzyme inhibition, NaPPS and CaPPS also have been shown to enter chondrocytes and bind to promoter proteins and alter gene expression of matrix metalloproteinases and possibly other mediators. In rat models of arthritis, NaPPS and CaPPS reduced joint swelling and inflammatory mediator levels in pouch fluids. Moreover, synoviocyte biosynthesis of high-molecular-weight hyaluronan, which is diminished in OA, was normalized when these cells were incubated with NaPPS and CaPPS or after intraarticular injection of NaPPS into arthritic joints. In rabbit, canine, and ovine models of OA, NaPPS and CaPPS preserved cartilage integrity, proteoglycan synthesis, and reduced matrix metalloproteinase activity. NaPPS and CaPPS stimulated the release of tissue plasminogen activator (t-PA), superoxide dismutase, and lipases from vascular endothelium while concomitantly decreasing plasma levels of the endogenous plasminogen activator inhibitor PAI-1. The net thrombolytic and lipolytic effects exhibited by NaPPS and CaPPS may serve to improve blood flow through subchondral capillaries of OA joints and improve bone cell nutrition. In geriatric OA dogs, NaPPS and CaPPS reduced symptoms, as well as normalized their thrombolytic status, threshold for platelet activation, and plasma triglyceride levels. These hematologic parameters were shown to be abnormal in OA animals before drug treatment. Similar outcomes were observed in OA patients when CaPPS or NaPPS were given orally or parenterally in both open and double-blind trials. CONCLUSIONS: The data presented in this review support the contention that NaPPS and CaPPS should be classified as SMOADs. However, additional long-term clinical studies employing methods of assessing joint structural changes will be needed to confirm this view.

Animals↗
PubMed1999

Cardiac reoperations in octogenerians.

OBJECTIVE: In recent years, satisfactory outcome of primary cardiac operation in octogenerians and increased ageing of cardiac surgical population in western hospitals have led to increased expectations and referrals for reoperation. Outcome of reoperation in this aged subset was analysed. METHODS: Consecutive 18 octogenerians (mean age 81.2 years, 10 men, eight women) undergoing cardiac reoperations from November 1989 through August 1998 were retrospectively reviewed. RESULTS: They represented 6.2% of all octogenerian cardiac surgical patients and 2.7% of all reoperations during the same period. Mean preoperative NYHA class was 3.4 and Parsonnet score was 29.4. The interval to reoperation was 114.5+/-11.96 (4-188) months. Priority was urgent in 11 and elective in seven patients. The procedures included four AVRs, five MVRs (including two associated TVAs), six CABGs and one each of MVR with CABG, AVR with CABG and AVR, MVR and CABG. Average graft/patient was 2.3. Mean ICU stay was 4.6+/-1.5 (1-28) days. There was one hospital death (5.5%) on 18 pod after MVR in an 83-year-old woman. Mean postoperative stay was 20.2+/-5.13 (8-93) days. There were three late deaths (17.6%)--at 32 months after MVR, at 44 and 63 months after CABG. Long-term survivors were 90% among men and 50% among women who were followed up for 42.7+/-6.9 (9-93) months. Mean Karnofsky score in survivors at 1 year of follow-up was 78.5+/-2.9. Despite continued medication in all survivors, mean current NYHA is 1.9 and most have improved lifestyle. CONCLUSIONS: Satisfactory outcome may be expected after cardiac reoperations in highly selected octogenerians. However, increased procedural risks, complications, hospital stay and slower convalescence during early follow-up may be anticipated, and will indicate very careful screening. These results indicate a need to reconsider the treatment policy in primary operation with regard to choice of graft conduits and prosthetic valves in other elderly patients.

Age Factors↗
PubMed1999

Structure of the lnlB leucine-rich repeats, a domain that triggers host cell invasion by the bacterial pathogen L. monocytogenes.

The L. monocytogenes protein lnlB activates phosphoinositide 3-kinase and induces phagocytosis in several mammalian cell types. The 1.86 A resolution X-ray crystal structure of the leucine-rich repeat domain of lnlB that is both necessary and sufficient to induce phagocytosis is presented here. The structure supports a crucial role for calcium in host cell invasion by L. monocytogenes and supplies a rationale for its function. Calciums are bound to the protein in an unusually exposed manner that suggests that the metals may act as a bridge between lnlB and mammalian cell surface receptors. The structure also identifies surfaces on the curved and elongated molecule that may constitute additional interaction sites in forming a bacterial-mammalian signaling complex.

Amino Acid Sequence↗