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

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Caribbean-wide decline in carbonate production threatens coral reef growth

This a post-print, author-produced version of an article accepted for publication in Nature Communications. Copyright © 2013 Nature Publishing Group . The definitive version is available at http://www.nature.com/ncomms/journal/v4/n1/full/ncomms2409.htmlGlobal-scale deteriorations in coral reef health have caused major shifts in species composition. One projected consequence is a lowering of reef carbonate production rates, potentially impairing reef growth, compromising ecosystem functionality and ultimately leading to net reef erosion. Here, using measures of gross and net carbonate production and erosion from 19 Caribbean reefs, we show that contemporary carbonate production rates are now substantially below historical (mid- to late-Holocene) values. On average, current production rates are reduced by at least 50%, and 37% of surveyed sites were net erosional. Calculated accretion rates (mm year(-1)) for shallow fore-reef habitats are also close to an order of magnitude lower than Holocene averages. A live coral cover threshold of ~10% appears critical to maintaining positive production states. Below this ecological threshold carbonate budgets typically become net negative and threaten reef accretion. Collectively, these data suggest that recent ecological declines are now suppressing Caribbean reef growth potential

Predicting Responses of Geo-ecological Carbonate Reef Systems to Climate Change: A Conceptual Model and Review

[Chapter Abstract] 230Coral reefs provide critical ecological and geomorphic (e.g. sediment production for reef-fronted shoreline maintenance) services, which interact in complex and dynamic ways. These services are under threat from climate change, requiring dynamic modelling approaches that predict how reef systems will respond to different future climate scenarios. Carbonate budgets, which estimate net reef calcium carbonate production, provide a comprehensive ‘snap-shot’ assessment of reef accretionary potential and reef stability. These budgets, however, were not intended to account for the full suite of processes that maintain coral reef services or to provide predictive capacity on longer timescales (decadal to centennial). To respond to the dual challenges of enhancing carbonate budget assessments and advancing their predictive capacity, we applied a novel model elicitation and review method to create a qualitative geo-ecological carbonate reef system model that links geomorphic, ecological and physical processes. Our approach conceptualizes relationships between net carbonate production, sediment transport and landform stability, and rates knowledge confidence to reveal major knowledge gaps and critical future research pathways. The model provides a blueprint for future coral reef research that aims to quantify net carbonate production and sediment dynamics, improving our capacity to predict responses of reefs and reef-fronted shorelines to future climate change.https://nsuworks.nova.edu/occ_facbooks/1116/thumbnail.jp

Crustose coralline algae can contribute more than corals to coral reef carbonate production

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: Data are available at https://github.com/JayCrlt/CCA_MethodsCode availability: Codes are available at https://github.com/JayCrlt/CCA_MethodsUnderstanding the drivers of net coral reef calcium carbonate production is increasingly important as ocean warming, acidification, and other anthropogenic stressors threaten the maintenance of coral reef structures and the services these ecosystems provide. Despite intense research effort on coral reef calcium carbonate production, the inclusion of a key reef forming/accreting calcifying group, the crustose coralline algae, remains challenging both from a theoretical and practical standpoint. While corals are typically the primary reef builders of contemporary reefs, crustose coralline algae can contribute equally. Here, we combine several sets of data with numerical and theoretical modelling to demonstrate that crustose coralline algae carbonate production can match or even exceed the contribution of corals to reef carbonate production. Despite their importance, crustose coralline algae are often inaccurately recorded in benthic surveys or even entirely missing from coral reef carbonate budgets. We outline several recommendations to improve the inclusion of crustose coralline algae into such carbonate budgets under the ongoing climate crisis.French Embassy - French Related Research Projects (F2RP)Agence Nationale de la Recherche (ANR)Royal Society of New Zealand Te Apārang

Avoiding Coral Reef Functional Collapse Requires Local and Global Action

oral reefs face multiple anthropogenic threats, from pollution and overfishing to the dual effects of greenhouse gas emissions: rising sea temperature and ocean acidification [1]. While the abundance of coral has declined in recent decades [2, 3], the implications for humanity are difficult to quantify because they depend on ecosystem function rather than the corals themselves. Most reef functions and ecosystem services are founded on the ability of reefs to maintain their three-dimensional structure through net carbonate accumulation [4]. Coral growth only constitutes part of a reef's carbonate budget; bioerosion processes are influential in determining the balance between net structural growth and disintegration [5, 6]. Here, we combine ecological models with carbonate budgets and drive the dynamics of Caribbean reefs with the latest generation of climate models. Budget reconstructions using documented ecological perturbations drive shallow (6-10 m) Caribbean forereefs toward an increasingly fragile carbonate balance. We then projected carbonate budgets toward 2080 and contrasted the benefits of local conservation and global action on climate change. Local management of fisheries (specifically, no-take marine reserves) and the watershed can delay reef loss by at least a decade under "business-as-usual" rises in greenhouse gas emissions. However, local action must be combined with a low-carbon economy to prevent degradation of reef structures and associated ecosystem services

A Bayesian Belief Network to assess rate of changes in coral reef ecosystems

It is crucial to identify sources of impacts and degradation to maintain functions and services that the physical structure of coral reef provides. Here, a Bayesian Network approach is used to evaluate effects that anthropogenic and climate change disturbances have on coral reef structure. The network was constructed on knowledge derived from the literature and elicited from experts, and parameterised on independent data. Evaluation of the model was conducted through sensitivity analyses and data integration was fundamental to obtain a balanced dataset. Scenario analyses, conducted to assess the effects of stressors on the reef framework state, suggested that calcifying organisms and carbonate production, rather than bioerosion, had the largest influence on the reef carbonate budgetary state. Despite the overall budget remaining positive, anthropogenic pressures, particularly deterioration of water quality, affected reef carbonate production, representing a warning signal for potential changes in the reef state