Contents of this Issue:
1. Science Highlight —
A New Groove for the Helix-Turn-Helix Motif...
(contact: John A. Tainer,
jat@scripps.edu )
Error-free DNA replication depends on the maintenance of the correct chemical structure of each component base. Bases with altered structures may mispair during the replication process, causing mutations. One common chemical alteration is the addition of an alkyl group to guanine, causing mispairing to thiamine during replication. The resulting G-C to A-T base pair mutation can be prevented if the protein alkylguanine-DNA alkyltransferase (AGT) locates and removes the alkyl group prior to replication. While AGT is a useful component of healthy cells, elevated levels in cancer cells can cause resistance to chemotherapy treatments that include alkylating agents. Knowledge of the structure and mechanism of AGT may lead to the development of inhibitors that could prevent cancer cells from acquiring resistance.
The crystal structures of AGT bound to alkylated DNA fragments, both pre- and
post- catalysis, were solved by scientists collaborating from The Scripps
Research Institute, Pennsylvania State University College of Medicine, and
Johns Hopkins University. To lock down the pre-catalytic form, they used an
inactive protein with a native substrate. To acquire the post-catalytic form,
crystals were grown of the active protein crosslinked to the DNA through an
alkylated guanine analog. In the resulting structures, the protein rotates the
phosphates of the DNA backbone to cause a rotation of the alkylated base into
the protein's active site. The researchers note their surprise that the protein
accesses the DNA through the minor groove, since all previous examples of
similar proteins show binding to the more easily accessible and
information-rich major groove. To learn more about this research, see:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/AGT.html
or
http://www-ssrl.slac.stanford.edu/research/highlights_archive/AGT.pdf
2. Science Highlight —
Surprising Ways of Binding Throw Clearer Light on Global Nitrogen Cycle
(contact: Michael E.P. Murphy,
memurphy@interchange.ubc.ca)
Nitric oxide (NO) is a small but powerful biologically active molecule that can protect or destroy cells. The bacterial enzyme that creates NO can, however, also turn nitrogen fertilizers into ozone-depleting NO and nitrous oxide, a greenhouse gas. Researchers at the University of British Columbia now have a better understanding of how that enzyme, nitrite reductase (NiR), works. Elitza Tocheva and Michael Murphy used SSRL's macromolecular crystallography facilities to study difficult-to-prepare crystal complexes of NiR bound to NO or to nitrite (which NiR turns into NO).
The results were surprising. NO and nitrite attach to a copper atom at an
active site in the enzyme. Both atoms in NO, a nitrogen and an oxygen, bind
directly to the copper, rather than the usual case in NO-metal binding where
just the nitrogen attaches to the metal. The novel NO-copper geometry may be
relevant to other kinds of copper-containing enzymes that play roles in
neurodegenerative diseases. Nitrite also bound to copper in NiR in an
unexpected way, with the nitrogen moved away from the plane of the nitrite and
Cu atoms. This makes the nitrogen atom tilt towards the active site.
Determining the structures also solved a puzzle: now scientists can imagine how
nitrite can be reduced to NO without having to do an unprecedented backflip at
the enzyme's active site. This insight into the structure of NiR could lead to
ways to inhibit its activity (to prevent release of environmentally dangerous
gases) or ways to use the enzyme to remove nitrogen from specific environments.
To learn more about this recent article in Science, see:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/NiR.html
or
http://www-ssrl.slac.stanford.edu/research/highlights_archive/NiR.pdf
3. DOE Funds New Ultrafast Science Center
(contact: Kelly Gaffney,
kgaffney@slac.stanford.edu)
The future of ultrafast electron and x-ray studies at SSRL received a significant boost with news of funding of a new grant from the Department of Energy Office of Basic Energy Sciences. This grant provides for funding of several key research areas which are a part of a new Ultrafast Science Center being started at Stanford in an effort that couples research activities at SSRL and campus departments. The coming of the Linac Coherent Light Source (LCLS), the world's first hard x-ray laser, and the Ultrafast Science Center will help ensure that Stanford and SSRL will be at the forefront of advances in the studies of ultrafast phenomena using x-rays and electrons. The Center will focus on ultrafast structural and electronic dynamics in materials science, the generation of attosecond laser pulses, and single molecule imaging during the first three years of operation. It is hoped that a future expansion of the scientific scope and effort will coincide with the completion of construction and commissioning of the LCLS in FY2007 and beyond.
4. Register for Annual Users' Meeting and
Workshops by October 14
(contact: Cathy Knotts,
knotts@slac.stanford.edu)
What a busy month — in October user operations resume, and then there's the 31st Annual SSRL Users' Meeting and Workshops. The Annual Users' Meeting on October 21-22, co-chaired this year by Mike Toney (SSRL) and Glenn Waychunas (LBNL), will feature presentations to help users incorporate new technology and make the most of SPEAR3 beam time as well as sessions on spectroscopy, scattering and diffraction; a keynote presentation on ultrafast x-ray science; a special session on the history and future of photoemission in memory of W.E. Spicer; and reports from young investigators and SSRL staff. The meeting also provides an excellent opportunity for users to interact with staff, SR equipment vendors, and other colleagues in numerous fields.
Users are encouraged to share their research results at the poster session on Thursday, October 21; abstracts received by October 6 will be included in the program material. In addition, the cost to attend the Awards Dinner will be waived for any graduate student submitting a poster for the graduate student poster competition.
Several workshops covering a wide range of topics will be held in conjunction with this meeting.
Workshops on Wednesday, October 20:
Workshop on Monday-Tuesday, October 25-26:
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5.
SPEAR Beam Line and User Operations Update
(contacts: Cathy Knotts,
knotts@slac.stanford.edu)
A significant amount of work occurred during the 2004 summer shutdown; specific beam line work included lead shielding for BL2-2; new slits and BPM for BL5; new shielding and new optics (M0 and M1 mirror and associated hardware) for BL6-2; masks and slits for BL10; and new graphite filters for BL11. Users operations resume on many beam lines the week of October 18 (see beam line and SPEAR operating schedules at http://www-ssrl.slac.stanford.edu/schedules/).
BL9 will be available in October 2004, but will be down from late December through late January for beam line upgrades, including: BL9-1 which will get new optics (I-beam mono); BL9-2 will get new optics (LN monochromator); and BL9-3 will get new slit jaws and masks. BL7-2 and BL10-2 will be available through June 2005, when the rebuild of all of BL7 is scheduled to begin in conjunction with earthquake/shielding work needed on the Building 120 shield wall which stretches from BL2 to BL10. Following this work during the summer 2005 shutdown, user operations are expected to resume on BL7-1, 7-2, 7-3, and 10-2 in the fall of 2005. BL3 will open after the Radiation Physics review and approval process; we anticipate that BL3-1 (LIGA) may be ready to resume operations in early 2005, and that BL3-3 (soft energy) may also be available in early 2005 with interim optics (final optics will be in place in 2006-2007). First light through the newly rebuilt BL5-1/5-2 experimental station was seen at the end of July 2004; this photoemission beam line is expected to be ready for users later in 2005. BL4-1/4-3 (XAS) will be closed through approximately 2006 when all of BL4 is expected to be ready for 500 mA operation.
SPEAR will continue to operate at 100 mA for the first user scheduling period in 2005 while beam line optical components are upgraded and radiation shielding is completed for higher currents. We anticipate that the current will be increased in periods of running beginning in 2005 with the details and schedule yet to be determined.
6.
On-Site Access Requirements for New and Returning Users
(contacts: Cathy Knotts,
knotts@slac.stanford.edu; Lisa Dunn, lisa@slac.stanford.edu)
User Information Form Submittal: SSRL is required to collect biographical information from every user in advance of their first scheduled visit during each run year (Oct-Jul). In order to comply with these requirements, SPOKESPERSONS of proposals at SSRL are required to provide contact information for all collaborators/experimenters who plan to be on-site to work under their proposals, and ALL USERS are required to submit the SSRL User Information Form 30 days before their first anticipated visit during each run year to either Cathy Knotts (X-ray/VUV lines) or Lisa Dunn (MC lines). http://www-ssrl.slac.stanford.edu/users/user_admin/user-info-form.pdf
For all on-site users who are not U.S. citizens, we must verify each user's
eligibility to be in the U.S. on an annual basis by reviewing passport, visa
and USCIS documentation (e.g., I-94, I-20, DS-2019/IAP-66) before issuing an ID
badge for unescorted site access. For all on-site users who were born in, are
citizens of, or represent organizations from certain foreign countries that the
U.S. government has identified as either sensitive* or state sponsors of
terrorism (SST)**, we must collect additional information and forward this to
the DOE through the Foreign Access Central Tracking System (FACTS) database so
that approval can be obtained from various government officials. Advance
approval is required before any users from SST countries can be allowed
unescorted access; this approval is currently taking >3 years in many cases.
http://www-ssrl.slac.stanford.edu/users/user_admin/fva_procedures.html
GERT Training: Entry onto the SSRL experimental floor, currently designated a Radiologically Controlled Area, requires General Employee Radiation Training (GERT) training and a dosimeter. If users have already completed GERT training from another facility, they must forward or bring a copy of the safety training certification in order to transfer that GERT training to SLAC. Users who have not already completed GERT will be required to complete this 2-3 hour computer-based training upon arrival (training is valid for 2 years). Please contact Jackie Robleto, jackie@slac.stanford.edu / 650-926-2079, to make an appointment to complete or transfer GERT training. http://www-group.slac.stanford.edu/esh/training/trainops/115.html
Guest House Reservations: Though not a requirement, the SLAC Guest House cannot be beat for comfortable lodging within a 2-minute walk to SSRL's experimental floor. Contact the SLAC Guest House to secure your reservations. http://www.stanford.edu/dept/hds/SLAC/reservations.html (Be sure to reference SSRL group block)
7. 3rd Annual Kids Day a Booming Success
(contact: Teresa Troxel,
ttroxel@ssrl.slac.stanford.edu)
SLAC hosted its 3rd Kids Day @ SLAC on Thursday, August 19, registering 234 boys and girls ages 9 to 16 years. Each kid attended 2 hours of workshop in the morning and the afternoon and a science lecture presented by Dr. Graham George (AKA Dr. Boom!). Each kid completed a hands-on project in the mechanical, welding and electronic workshops. There were also science workshops in astrophysics, waves and biology. Other technical workshops included magnetics, cryogenics, radiation, vacuum and metrology. The most unique aspect of the SLAC Kids Day is that each kid has the opportunity to work one-on-one with a technician, engineer and/or scientist. The program has been rewarding for both the kids and the staff volunteers! see also: http://www2.slac.stanford.edu/tip/2004/sep03/kids.htm
8.
BL11-3, SSRL's Newest Beam Line for Materials Science
(contact: Mike Toney,
mftoney@slac.stanford.edu)
This new beam line, utilizing a milli-radian of beam on the BL11 26-pole, 2.0-T wiggler insertion device, is a quasi-fixed energy beam line designed for shared use by the macromolecular crystallography and materials scattering communities. The beam line employs an off-cut, side scattering, focusing Si(311) crystal monochromator optimized at approximately 12,700 eV. Vertical focusing is provided by a 1 m long Rh-coated Si mirror located downstream of the monochromator. The vertical focused beam size at the sample position is less than 0.1 mm, while the horizontal focused beam size is 2.5 mm due to the effective source size. Both horizontal and vertical beam sizes can be set with slits. The beam line has a kappa diffractometer, controlled with SUPER, and the diffracted beam is analyzed with either Soller slits or two adjustable Huber slits. We are presently using a Bicron detector, but plan to implement a fast Rontec Si-drift detector, which provides approximately 200 eV energy resolution.
The beam line is optimized for thin film scattering, specular and off-specular reflectivity, and other general single crystal diffraction. A vacuum chuck and He environment are available for samples, but at present only room-temperature experiments are possible. To date, this has been used to study structure in organic, metal, and semiconductor thin films and multilayers and charge-density waves in Re-Te3.
Materials scattering users may also be interested in participating in the
October 20 workshop which will include hands-on practice at BLs 11-3, 7-2, and
2-1. In addition to basic techniques of diffractometer alignment, users will
learn how to do specific measurements on each station such as grazing incidence
scattering, specular reflectivity, powder diffraction and anomalous scattering.
There will also be demonstrations of the recently acquired 900°C furnace.
http://www-conf.slac.stanford.edu/ssrl/2004/reg/reg.asp
9.
Changes for VWP Travelers — Machine Readable and Biometric Passport
Requirements Take Effect in 2004 and 2005
After October 26, 2004, travelers to the U.S. under the Visa Waiver Program (VWP) will be required to have machine-readable passports (last year, the deadline of October 1, 2003, was postponed until October 26, 2004). VWP countries, originally scheduled to issue tamper-resistant passports containing biometric identifiers by October 26, 2004, have been granted a one-year extension (President Bush signed H.R. 4417/Public Law 108-299 in August extending the biometric passport deadline to October 26, 2005). VWP travelers with passports issued on or after October 25, 2005 will be required to present biometric passports when entering the U.S. The extension gives the U.S. an extra year to install equipment capable of scanning machine-readable, tamper-resistant passports that contain biometric identifiers. To mitigate security concerns related to this extension, the U.S. Department of Homeland Security will begin enrolling VWP travelers through the U.S. Visitor and Immigrant Status Indicator Technology (US-VISIT) program at all airports and seaports on or about September 30, 2004 (the US-VISIT process requires two digital index finger scans and a digital photograph from travelers to verify their identity). By the end of 2005, all domestically produced U.S. passports will also incorporate biometric identifiers. To view the Department of State press release on this issue, visit: http://www.state.gov/r/pa/prs/ps/2004/35066.htm
10. User Research Administration Announcements
(contacts: Cathy Knotts,
knotts@slac.stanford.edu; Lisa Dunn, lisa@slac.stanford.edu)
Beam time request form(s) for active X-ray and VUV proposals for the second
scheduling period of the FY05 experimental run which is scheduled to begin in
January 2005 and run through early April 2005 are due before October 22. Beam
time requests can be submitted by fax at 650-926-3600 or electronically via our
website.
http://www-ssrl.slac.stanford.edu/users/user_admin/xray_btrf.html (X-ray)
http://www-ssrl.slac.stanford.edu/users/user_admin/vuv_btrf.html (VUV)
If your current proposal is getting close to its expiration date or if you plan
additional experiments, please consider submitting new X-ray and VUV proposals
by the November 1, 2004 deadline or a new Macromolecular Crystallography
proposal by the December 1, 2004 deadline.
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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