Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.11 (
CD10
)
9,792
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Perturbations of stromal-epithelial interactions in the developing tumour can contribute to cancer invasion and metastasis. The structurally related metallopeptidases endothelin-converting enzyme (ECE) and
neutral endopeptidase
(
NEP
) contribute sequentially to the synthesis and inactivation of ET-1, a mitogenic peptide that has been shown to affect tumour behaviour. This study has investigated the interaction between metastatic tumour epithelial cells, which lack
NEP
, and stromal cells, which we have shown to express ECE-1 (stromal-epithelial interactions), using Matrigel invasion chambers. The epithelial cell lines utilised in this study include androgen-sensitive LNCaP, androgen-independent PC-3, Du145 and recently established
PNT
-1a, PNT2-C2 and P4E6 prostate cell lines. Specific inhibition of endogenous ECE-1 activity in stromal cells reduced PC-3 and Du145 invasion by 70 and 50%, respectively. Addition of recombinant
NEP
to inactivate endogenous mitogenic peptides resulted in 50 and 20% reductions in invasion in PC-3 and Du145 cells, respectively. Neutral endopeptidase effects were reversed in the presence of thiorphan, a specific
NEP
inhibitor. Supplementation of defined media with bradykinin and ET-1 significantly increased PC-3 invasion by 40 and 50%, respectively. Du145 cell invasion increased by approximately 100% on adding ET-1. These studies implicate the metallopeptidases
NEP
and ECE-1 as mediators of prostate cancer invasion via a stromal/epithelial interaction.
...
PMID:Stromal-epithelial interactions influence prostate cancer cell invasion by altering the balance of metallopeptidase expression. 1508 88
Lysostaphin, a bacteriolytic toxin from Staphylococcus simulans, is a Zn
2+
-dependent
endopeptidase
that cleaves pentaglycine cross-bridges found in peptidoglycan of certain Staphylococci. Here, we have investigated a critical influence of Zn
2+
ions on lysostaphin-induced bioactivity. Initially, we succeeded in producing a large amount with high purity of the 28-kDa His-tagged mature lysostaphin via soluble expression in Escherichia coli and subsequent purification via immobilized-Ni
2+
affinity chromatography (IMAC). The purified monomeric bacteriocin exhibited concentration-dependent bioactivity against S. aureus and its methicillin-resistant strain through cell-wall hydrolysis rather than membrane perturbation. Following pre-incubation of the purified lysostaphin with exogenous Zn
2+
, a marked inhibition in staphylolytic activity was observed. When the pre-mixture was exposed to 1,10-phenanthroline (
PNT
, a Zn
2+
-chelator), the adverse effect of the exogenous Zn
2+
on bioactivity was greatly decreased. Conversely, lysostaphin pre-treated with excess
PNT
retained relatively high bioactivity, indicating ineffective chelation of
PNT
to detach the catalytic Zn
2+
from the active-site pocket. Structural analysis of the lysostaphin-catalytic domain together with amino acid sequence alignments of lysostaphin-like endopeptidases revealed a potential extraneous Zn
2+
-binding site found in close proximity to the Zn
2+
-coordinating active site. Overall our results provide more insights into an adverse influence of exogenous Zn
2+
ions on staphylolytic activity of the purified Zn
2+
-dependent
endopeptidase
lysostaphin, implicating the presence of an extraneous inhibitory metal-binding site.
...
PMID:Purification and characterization of the antibacterial peptidase lysostaphin from Staphylococcus simulans: Adverse influence of Zn
2+
on bacteriolytic activity. 2994 58
