Contents of this Issue:
1. Science Highlight — Fighting
Antibiotic Resistance: New Drug Target Mapped
(contact: Robert Scott,
scott@chem.uga.edu)
Antibiotics and the bacteria they attack are engaged in a constant race to out-evolve one another. An antibiotic is effective against specific bacteria only so long before the random mutations that all bacteria undergo make them resistant to that particular drug. Recently, scientists from the University of Georgia, Utah State University, and Guilford Pharmaceuticals carried out studies at SSRL that could enable drug designers to pull ahead, at least for a while, by developing a new class of antibiotics.
Their work explored a novel antibacterial target: a step in the recipe most bacteria use to create the rigid wall that surrounds and protects individual bacterial cells. Two important components of the cell wall, mDAP and lysine, are synthesized in bacteria by the enzyme DapE. Deleting the gene that encodes DapE has been shown to be lethal to certain bacteria, including the strain that causes stomach ulcers and that appears to be a major cause of stomach cancer, so inhibiting the DapE enzyme looks like a promising approach for drug designers. Because mammals use a different recipe to make their cell walls, an antibiotic that inhibits the DapE enzyme should be toxic to bacteria but not to human cells.
The researchers used a technique possible only with synchrotron light (analysis of extended x-ray absorption fine structure or EXAFS) to map the atomic neighborhood of the chemically active part of the DapE enzyme. This information is important for identifying a chemical component that can lock onto this site and prevent the enzyme from doing its job in production of the cell wall. The investigators also obtained additional information useful in drug design: a view of enzyme bound to inhibiting molecules and a glimpse of the enzyme in action.
For more information on this work see:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/dape.html
or
http://www-ssrl.slac.stanford.edu/research/highlights_archive/dape.pdf
2. The Structure of the First Coordination Shell
in Water
(contact: Anders Nilsson,
nilsson@slac.stanford.edu)
Water is the key molecule for our existence on this planet and it is involved in a great number of biological, geological and chemical processes. Knowledge about the hydrogen-bonded network structure in water is essential for understanding its unusual chemical and physical properties. In its condensed phase, ice (Ih) e.g., each water molecule is coordinated by four others in a semi-tetrahedral arrangement forming an ordered crystal structure. In contrast, in liquid water a statistical distribution of different coordinations can be assumed due to the dynamical motion of the atoms causing the hydrogen bonds to break and reform on a picosecond (ps)-time scale. In a recent report, Wernet et al. [Science Express Reports, 10.1126/science.1096205 (2004)] studied the first hydration shell of a water molecule in bulk liquid water by probing its electronic structure using X-ray Absorption Spectroscopy (XAS) and X-ray Raman Scattering (XRS). From carefully designed experimental models as well as theoretical spectra simulations, with results contrary to molecular dynamics simulations, Wernet and coworkers conclude that the local surrounding of a water molecule in liquid water resembles that in the topmost layer of ice, i.e., it is characterized by a substantial number of broken hydrogen bonds. The results of the study shows that water, on the probed sub-femtosecond time-scale, consists mainly of structures with two strong hydrogen bonds, one donating and one accepting, compared to the four-hydrogen-bonded tetrahedral structure in ice. This implies that most molecules are arranged in strongly hydrogen-bonded chains or rings embedded in a disordered cluster network connected mainly by weak hydrogen bonds. See http://www-ssrl.slac.stanford.edu/structureofwater.html for links to the paper in Science, press release, and a more detailed description of the results.
3. User Operations Update
(contact: Cathy Knotts,
knotts@slac.stanford.edu)
Several more beam lines have opened during the past month including 11-1, 11-2,
11-3, 7-2 and 2-3. SPEAR3 has delivered an average of 95% of the beam
time scheduled for users so far, this despite a one-day down caused by an RF
power failure in the injector earlier this week. Top offs are still being
scheduled four times a day at 6 am, 12 pm, 6 pm and 12 am, but the fill time is
only about 3 minutes. One user has commented "The fills are too short to even
get a cup of coffee, much less go out for a meal". Announcements will be made
before each fill, and users may request a slight delay on the fill time to
coordinate their scans and maximize their data taking. SPEAR status updates are
available on the website:
http://www-ssrl.slac.stanford.edu/talk_display.html
Due to issues related to the SLAC electrical power contract, the user run will
end on July 31 at 10 pm, rather than August 2 at 6 am as originally projected.
The SPEAR operating schedule is available on the website:
http://www-ssrl.slac.stanford.edu/schedules/
4.
SPEAR3 Improved Performance Benefiting Users
(contact: Piero Pianetta,
pianetta@ssrl.slac.stanford.edu)
While we do not expect to schedule regular user operations at higher currents
(up to 500 mA) until the FY2005 experimental run, we are already seeing
quantifiable improvements in terms of beam stability and brightness, etc., that
show the clear benefits of the new SPEAR3 accelerator.
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5. SiWeds Semiannual Meeting at SSRL
(contact: Piero Pianetta,
pianetta@ssrl.slac.stanford.edu)
On April 16-17, SSRL hosted the semiannual meeting of the National Science Foundation sponsored Silicon Wafer Engineering Defect Science Center (SiWeds) at SLAC. This center consists of a partnership of 8 universities with major semiconductor companies working in the areas of wafer manufacturing, semiconductor processing equipment, photovoltaics and integrated circuits. The meeting had forty participants covering an agenda ranging from defect reduction in wafer substrates to new developments in the area of silicon-on-insulator technologies. Synchrotron radiation use at the ALS and SSRL is playing an important role in the research to study precipitates in and contaminants on the silicon wafers. For more information, see http://www.siweds.com
6. Pre-Approval Required for On-Site Users
from SST Countries
(contact: Cathy Knotts,
knotts@slac.stanford.edu)
DOE facilities are required to collect and enter biographical information on
users from foreign countries that the government has identified as sensitive or
state sponsors of terrorism (SST) into a central database before user ID badges
can be issued. For users from SST countries, advance approval is required
before any on-site visits. Since this approval process is taking 6-8 months,
users from SST countries need to submit this information by this time in order
to secure the necessary approvals. We regret the difficulties experienced by
users in complying with this requirement, and we appreciate your cooperation.
http://www-ssrl.slac.stanford.edu/users/user_admin/user-info-form.pdf
7. Radiation Safety Training Needed for 2004
— Send GERT Documentation before Visit to Speed Up Training Transfer
(contact: Cathy Knotts,
knotts@slac.stanford.edu)
We are monitoring experimental areas during the first several months of steady
running with SPEAR3 to demonstrate that radiation outside the shield wall is
well below DOE limits. As a conservative measure and as required by radiation
safety policies, the experimental floor at SSRL has been declared a
Radiologically Controlled Area (RCA) during this time. General Employee
Radiation Training (GERT) and the prerequisite, Employee Orientation to
Environment, Safety and Health (EOESH) are required for all SSRL users before
they can be issued an ID badge and dosimeter to access RCA experimental areas.
Users need to make advance appointments to use one of the four computer-based
training terminals in the user administration office; EOESH and GERT training
takes 2-3 hours to complete. To facilitate more rapid training and testing,
users are encouraged to review the study guides and Safety Basics summary
before they arrive:
http://www.slac.stanford.edu/esh/training/study_guides/EOESH.pdf
and
http://www.slac.stanford.edu/esh/training/study_guides/GERT.pdf
http://www-ssrl.slac.stanford.edu/users/user_admin/Safety_Basics.pdf
To transfer radiation safety training completed at another DOE facility, users should send training certification to Cathy Knotts (knotts@slac.stanford.edu; fax 650-926-3600) or Lisa Dunn (lisa@slac.stanford.edu; fax 650-926-3600) in advance of their scheduled visit. A brief SLAC-specific safety orientation is still required.
8. State Your Affiliation with SSRL when
Making Guest House Reservations
(contact: Cathy Knotts,
knotts@slac.stanford.edu)
A block of rooms have been arranged at the SLAC Guest House during the SSRL user run and other SSRL events, so please identify your affiliation with "SSRL" when making reservations to take advantage of these rooms. Users who have stayed at the Guest House give it the thumbs up: "The guest house is really convenient!!" Raquel Lieberman, Northwestern University; "New guest house is excellent" Gary Long, Univ. Missouri; "The new Guest House is very nice and extremely convenient to use. We all liked it very much, and will continue to use this for accommodations." C. David Stout, The Scripps Research Institute. http://www.stanford.edu/dept/hds/SLAC/
9. User Administration Update
(contact: Cathy Knotts,
knotts@slac.stanford.edu)
New X-Ray/VUV proposals are due May 1. Additional mechanisms for obtaining
x-ray/vuv beam time on SPEAR3 include Rapid Turnaround XAS Proposals (to
accommodate straightforward x-ray absorption spectroscopy experiments that
require only small amounts of beam time) and Letter of Intent Proposals (to
accommodate particularly novel ideas throughout the year). Instructions for
submitting proposals and the associated forms can be found at:
http://www-ssrl.slac.stanford.edu/users/user_admin/guide.html
__________________________________________________________________________
SSRL Headlines is published electronically monthly to inform SSRL users, sponsors and other interested people about happenings at SSRL. SSRL is a national synchrotron user facility operated by Stanford University for the U.S. Department of Energy Office of Basic Energy Sciences. Additional support for the structural biology program is provided by the DOE Office of Biological and Environmental Research, the NIH National Center for Research Resources and the NIH Institute for General Medical Sciences. Additional information about SSRL and its operation and schedules is available from the SSRL WWW site.
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