Structural highlights
Function
CBPA4_HUMAN Metalloprotease that could be involved in the histone hyperacetylation pathway.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Treatment of advanced stages of prostate carcinoma with histone-deacetylase inhibitors entails expression of human procarboxypeptidase-A4 (hPCPA4). The three-dimensional structure of hPCPA4 has been solved and shows the features of related metallocarboxypeptidase zymogens, with a preformed alpha/beta/-hydrolase active-enzyme moiety (hCPA4) and an inhibiting pro-domain (PD). The protease moiety recalls a sphere, out of which a spherical cone has been cut. This results in a funnel-like structure, at the bottom of which the active-site cleft resides. The border of this funnel is shaped by loops, which are responsible for the interaction with the PD, characterised by a large interface area and relatively few contacts. Such an inhibitory mode is evocative of the recently reported structure of the human inhibitor latexin in its complex with hCPA4. The main contacting structure of latexin is similar to the one employed for PD inhibition. In both cases, active-site blocking relies mainly on a loop provided by the central part of a beta sheet.
Detailed molecular comparison between the inhibition mode of A/B-type carboxypeptidases in the zymogen state and by the endogenous inhibitor latexin.,Garcia-Castellanos R, Bonet-Figueredo R, Pallares I, Ventura S, Aviles FX, Vendrell J, Gomis-Rutha FX Cell Mol Life Sci. 2005 Sep;62(17):1996-2014. PMID:16091843[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Huang H, Reed CP, Zhang JS, Shridhar V, Wang L, Smith DI. Carboxypeptidase A3 (CPA3): a novel gene highly induced by histone deacetylase inhibitors during differentiation of prostate epithelial cancer cells. Cancer Res. 1999 Jun 15;59(12):2981-8. PMID:10383164
- ↑ Garcia-Castellanos R, Bonet-Figueredo R, Pallares I, Ventura S, Aviles FX, Vendrell J, Gomis-Rutha FX. Detailed molecular comparison between the inhibition mode of A/B-type carboxypeptidases in the zymogen state and by the endogenous inhibitor latexin. Cell Mol Life Sci. 2005 Sep;62(17):1996-2014. PMID:16091843 doi:10.1007/s00018-005-5174-4
