Navigation Links
Chemists document workings of key staph enzyme -- and how to block it
Date:1/18/2011

CHAMPAIGN, Ill. Researchers have determined the structure and mechanism of an enzyme that performs the crucial first step in the formation of cholesterol and a key virulence factor in staph bacteria.

Chemists at the University of Illinois and collaborators in Taiwan studied a type of enzyme found in humans, plants, fungi, parasites, and many bacteria that begins the synthesis of triterpenes one of the most abundant and most ancient classes of molecules. Triterpenes are precursors to steroids such as cholesterol.

"These enzymes are important drug targets," said chemistry professor Eric Oldfield, who co-led the study. "Blocking their activity can lead to new cholesterol-lowering drugs, antibiotics that cure staph infections, and drugs that target the parasites that cause tropical maladies such as Chagas disease a leading cause of sudden death in Latin America."

For the study, the team picked a representative enzyme, dehydrosqualene synthase (CrtM), from the Staphylococcus aureus bacterium. Staph is one of the most common, yet notoriously hard to kill, bacterial infections. A key reason for staph's resilience is a golden-colored coating called staphyloxanthin that protects it from the body's immune system. CrtM catalyzes the first reaction in making staphyloxanthin, so inhibiting it would strip the bacteria of their protective coats and leave them vulnerable to attack by white blood cells.

The researchers already knew what CrtM looked like and its end product, but they didn't know how the enzyme did its job. Uncovering the mechanism of action would enable scientists to design better inhibitors, and even tailor them to other targets.

The team crystallized the enzyme and soaked it with intermediates and inhibitors. They then studied the complex structures by X-ray crystallography using the synchrotron at the Advanced Photon Source at Argonne National Laboratory.

They found that CrtM performs a two-step reaction, individually removing two diphosphate groups from the substrate. The substrate switches between two active sites within the enzyme as the reaction progresses. The most effective inhibitors bind to both sites, blocking the enzyme from any action.

"The leads that people have been developing for treating these diseases really haven't had any structural basis," said Oldfield, also a professor of biophysics. "But now that we can see how the protein works, we're in a much better position to design molecules that will be much more effective against staph infections and parasitic diseases, and potentially, in cholesterol-lowering."


'/>"/>

Contact: Liz Ahlberg
eahlberg@illinois.edu
217-244-1073
University of Illinois at Urbana-Champaign
Source:Eurekalert  

Related biology news :

1. US launches International Year of Chemistry Feb. 1 with panel of world-renowned chemists
2. Chemists concoct new agents to easily study critical cell proteins
3. Team of chemists produces biodiesel at their university, using used cooking oil as a basis
4. Brown University chemists simplify biodiesel conversion
5. Scripps researchers, UCSD chemists to create center devoted to chemistrys influence on climate
6. Caltech chemists develop simple technique to visualize atomic-scale structures
7. DNA puts Stanford chemists on scent of better artificial nose
8. MIT chemists design new way to fluorescently label proteins
9. Colorado State University biochemists study how chromosomes unravel to let genes do their jobs
10. Chemists influence stem-cell development with geometry
11. Behavior of single protein observed in unprecedented detail by Stanford chemists
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Chemists document workings of key staph enzyme -- and how to block it
(Date:3/23/2016)... Massachusetts , March 23, 2016 /PRNewswire/ ... im Interesse erhöhter Sicherheit Gesichts- und Stimmerkennung ... Xura, Inc. (NASDAQ: MESG ), ... bekannt, dass das Unternehmen mit SpeechPro zusammenarbeitet, ... aus der Finanzdienstleistungsbranche, wird die Möglichkeit angeboten, ...
(Date:3/22/2016)... , PROVO and ... Newborn Screening Ontario (NSO), which operates the highest sample ... molecular testing, and Tute Genomics and UNIConnect, leaders in ... respectively, today announced the launch of a project to ... (NGS) testing panel. NSO has been ...
(Date:3/18/2016)... --> --> Competitive Landscape ... Vehicles, Physical infrastructure and Perimeter Surveillance & Detection Systems ... market and the continuing migration crisis in the ... has led visiongain to publish this unique report, which is ... & security companies in the border security market and ...
Breaking Biology News(10 mins):
(Date:5/4/2016)... ... 2016 , ... PBI-Gordon Corporation is pleased to announce Doug Obermann has been ... career at PBI-Gordon in February 1988, after finishing his masters in agronomy from Iowa ... customer service to national product manager, to helping develop, name and launch many of ...
(Date:5/3/2016)... ... 2016 , ... In a list published by the Boston Business Journal, ... companies; a small percentage of the state's 615,000+ small businesses. The list examined companies ... revenue from 2012 to 2015. , As this award comes on the ...
(Date:5/3/2016)... ... May 03, 2016 , ... ... the sensor and data driven conferences, will take place on June 7-8, 2016, at the New ... Vidya Raman-Tangella on incorporating technology -- including AR/VR, machine learning, apps, robotics and AI ...
(Date:5/3/2016)... ... 03, 2016 , ... Nashville Fertility Center has joined a ... reproductive endocrinologists, including Dr. George Hill at Nashville Fertility Center, created ... build families. , Ovation Fertility is a nationwide network of leading fertility centers ...
Breaking Biology Technology: