Impact of casinos on residential property values: Henderson, Nevada

This thesis examines whether residential property values are affected by proximity to gaming establishments. Using a sample of houses from Henderson, Nevada, a hedonic price model is employed to relate residential sales prices to individual housing characteristics, including proximity to the nearest gaming establishment. Results indicate that proximity to gaming establishments do indeed lower residential property values. Further, it appears that larger gaming establishments have a larger impact on prices than smaller ones in Old HenderSo

S28 peptidases: lessons from a seemingly 'dysfunctional' family of two

<p>Abstract</p> <p>A recent paper in <it>BMC Structural Biology </it>reports the crystal structure of human prolylcarboxypeptidase (PRCP), one of the two members of the S28 peptidase family. Comparison of the substrate-binding site of PRCP with that of its family partner, dipeptidyl dipeptidase 7 (DPP7), helps to explain the different enzymatic activities of these structurally similar proteins, and also reveals a novel apparent charge-relay system in PRCP involving the active-site catalytic histidine.</p> <p>See research article: <url>http://www.biomedcentral.com/1472-6807/10/16/</url></p> <p>Commentary</p> <p>The S28 serine peptidase family is something of an enzymatic odd couple. While showing low sequence similarity to all proteins except each other, the two known family members appear to be at odds functionally; one, prolylcarboxypeptidase (PRCP), is a carboxypeptidase that cleaves single hydrophobic residues from the carboxyl termini of proteins that end with a Pro-X motif (where X is any hydrophobic amino acid), while the other, human dipeptidyl peptidase (DPP7), is an aminopeptidase that cleaves amino-terminal X-Pro dipeptides. The structural basis of this orthogonal specificity would undoubtedly be interesting, and a recent report in <it>BMC Structural Biology </it>from the Merck Global Structural Biology group (Soisson <it>et al</it>. <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>) has now met that expectation. In addition they reveal a new wrinkle to the iconic catalytic triad common to most serine hydrolases.</p> <p>The practical pharmaceutical interest in both these enzymes as potential drug targets is at present speculative. PRCP can inactivate a number of peptide hormones, such as angiotensin II, III and prekallikrein, implicating a role for the enzyme in hypertension, tissue proliferation and smooth-muscle growth. These properties suggest that this enzyme may well be a useful target for hypertension and anti-inflammatory therapy <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>. Another (non-S28 family) dipeptidyl dipeptidase (DPP4) is a major drug target in type 2 diabetes, and Merck has already developed a successful inhibitor of DPP4, the anti-hyperglycemic drug sitagliptin, for the treatment of type 2 diabetes. The DPP enzymes are rich in biological functions and other drug targets emerging from the group are possible <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>.</p

In Situ Kinase Profiling Reveals Functionally Relevant Properties of Native Kinases

SummaryProtein kinases are intensely studied mediators of cellular signaling, yet important questions remain regarding their regulation and in vivo properties. Here, we use a probe-based chemoprotemics platform to profile several well studied kinase inhibitors against >200 kinases in native cell proteomes and reveal biological targets for some of these inhibitors. Several striking differences were identified between native and recombinant kinase inhibitory profiles, in particular, for the Raf kinases. The native kinase binding profiles presented here closely mirror the cellular activity of these inhibitors, even when the inhibition profiles differ dramatically from recombinant assay results. Additionally, Raf activation events could be detected on live cell treatment with inhibitors. These studies highlight the complexities of protein kinase behavior in the cellular context and demonstrate that profiling with only recombinant/purified enzymes can be misleading

Expanding the Number of ‘Druggable’ Targets: Non‐Enzymes and Protein–Protein Interactions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95062/1/cbdd.12066.pd