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Protein
Crystallography Newsletter
Volume 1, No. 9, October 2009
In
this issue:
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Continuing
Education Webinar
Taking
the edge off: The softer side of in-house SAD phasing
Presenter: Joseph D. Ferrara, Ph.D.
November 19th at 10:00 AM EST
(15:00 GMT)
Click
here to register
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ACTOR sample
changing robot
(with a Saturn 944+ CCD detector in lower image).
 
CMTP is jointly
directed by Prof.
Tom Blundell (left) and Prof.
Ashok Venkitaraman (right).
CCP4
Study Weekend (6th - 8th January 2010)
"From Crystal to Structure with CCP4"
Click on image
or here
to take the one question survey.
André Guinier
© IUCr:Creative Commons attribution.
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Crystallography
in the news
October
24, 2009. Structural studies undertaken by a team, under the
leadership of Dr.
Dierk Niessing of the Helmholtz Zentrum München and the Gene
Center at Ludwig-Maximilians-Universität (LMU) in Munich, have
now determined the three-dimensional
structure of Pur-alpha and gained insights into the molecular
function of the protein behind fragile X tremor/ataxia syndrome (FXTAS).
October 21, 2009. Rice University scientists, led by Prof.
Jane Tao, have won a $1.5 million, 4 year grant from the
National Institutes of Health (NIH) to scrutinize the influenza A
virus for clues that could lead to more effective antiviral drugs.
Investigations will focus on the form
and function of the nucleoprotein (NP), one of fewer than a
dozen proteins encoded by the flu virus.
October 7, 2009. This year's Nobel
Prize in Chemistry was awarded to Venkatraman
Ramakrishnan, Thomas
A. Steitz and Ada
E. Yonath for using X-ray crystallography to elucidate the
molecular structure and function of the ribosome.
October 2, 2009. Scientists from the Lawrence Berkeley National
Laboratory and the Scripps Research Institute, led by John
Tainer and Paul
Russell respectively, have uncovered the role played by the
least-understood part of a first-responder molecule - a protein
complex called Mre11-Rad50-Nbs1
(or MRN for short) - that rushes in to bind and repair breaks in
DNA strands, a process that helps people avoid cancer.
October 1, 2009. Research groups at the European Molecular Biology
Laboratory (EMBL), the Institut de Biologie Structurale (IBS) and
the Institut Albert Bonniot - respectively led by Christoph
Müller, Carlo
Petosa and Saadi
Khochbin - have discovered a new
way to read the histone code. Their work shows how a protein
found only in developing sperm cells, Brdt, directs tight
re-packaging of sperm DNA.
Screen
more crystals with less effort
As structural biology projects have become more
challenging, it has also become more difficult (in many cases) to
get good diffracting crystals. Often it is necessary to screen
many crystals to find one that diffracts well or in order to
determine the best cryo protection conditions.
The Rigaku ACTOR™
sample changing robot is designed to automate the tedious process
of mounting and screening crystals. Automated sample mounting also
provides the added benefit of a reproducible mount and recovery
process that minimizes the potential for crystal damage and ice
formation that sometimes occurs with hand mounts.
ACTOR
is a complete system that has been continuously developed over the
past eight years to provide the most comprehensive and complete
commercial solution for automated sample mounting and screening.
Accurate automatic sample centering, optimized sample handling and
storage, and a software control package with integrated screening,
ranking and data collection functions makes ACTOR
the ideal sample mounting robot for the home X-ray lab or
synchrotron beamline.
Request
a copy of the ACTOR brochure or view a video
of ACTOR.
Lab
spotlight: What is CMTP?
The Cambridge
Molecular Therapeutics Programme (CMTP) is an
interdisciplinary initiative at the University of Cambridge,
jointly directed by Professors Ashok
Venkitaraman and Tom
Blundell, that seeks to address the limited repertoire of
molecular targets accessible to conventional methods for lead
discovery and the high attrition rate during early clinical
development in therapeutic areas such as oncology. The CMTP
harnesses a unique and interdisciplinary spectrum of leading
academic expertise in Cambridge for the discovery and development
of drugs against cancer and infectious diseases.
Useful
links for crystallography
MACiE,
which stands for Mechanism, Annotation and Classification in
Enzymes, is a collaborative project between the Mitchell Group at
the Unilever Centre for Molecular Informatics part of the
University of Cambridge and the Thornton Group at the European
Bioinformatics Institute. MACiE currently contains 223 fully
annotated enzyme reaction mechanisms, which comprise 218 EC
numbers (161 EC sub-subclasses) and 310 distinct CATH codes.
Science
Podcast interview with Venki Ramakrishnan discussing two
papers (vide infra) regarding the structure of
ribosomes - Schmeing et al. and Gao et al. (16 October 2009).
Selected
recent crystallographic papers
The Structure of the Ribosome with Elongation Factor G Trapped
in the Posttranslocational State. Y. Gao, M. Selmer, C.M. Dunham,
A. Weixlbaumer, A.C. Kelley and V. Ramakrishnan. Science,
DOI: 10.1126/science.1179709 (published online: October 15,
2009).
The Crystal Structure of the Ribosome Bound to EF-Tu and
Aminoacyl-tRNA. T.M. Schmeing, R.M. Voorhees, A.C. Kelley, Y. Gao,
F.V. Murphy, J.R. Weir and V. Ramakrishnan. Science,
DOI: 10.1126/science.1179700 (published online: October 15,
2009).
Template strand scrunching during DNA gap repair synthesis by
human polymerase. M. Garcia-Diaz, K. Bebenek, A.A. Larrea, J.M.
Havener, L. Perera, J.M. Krahn, L.C. Pedersen, D.A. Ramsden and
T.A. Kunkel. Nature
Structural & Molecular Biology 16,
967-972 (2009).
An epistatic ratchet constrains the direction of glucocorticoid
receptor evolution. J.T. Bridgham, E.A. Ortlund and J.W. Thornton.
Nature
461, 515-519 (2009).
Book
review: Small-Angle Scattering of X-rays
by André Guinier and Gérard Fournet; translated
by Christopher B. Walker
Published in 1955, this book is long out of print
and quite difficult to find. Fortunately, Dr. Angela Criswell
located a copy for this retrospective review. Given that SAXS is
such a "hot topic" these days, it was remarkable to find
that this old tome is still a relevant and useful reference for
researchers today.
To frame the perspective of the authors, it is notable that they
opined (in chapter 6) that "These remarks explain why the
study of proteins [dilute solutions] offers one of the best
applications on this method. As a matter of fact, a large number
of investigations have already been carried out on proteins, as is
shown in the bibliography at the end of the text. We believe that
it is in this field that small-angle scattering can give the most
valuable and important results from a general point of view."
We are coming up on the 50th anniversary of the publication of Structure
of Hæmoglobin: A Three-Dimensional Fourier Synthesis at 5.5 Å.
Resolution, Obtained by X-Ray Analysis. [Nature 185, 416-422
(1960)] by Perutz, Rossmann, Cullis, Muirhead, Will and North.
Guinier and Fournet did not foresee the explosion in protein
structure that would start five years later. Yet, it is quite
interesting that, 55 years after the publication, structural
biologists have come back to SAXS as a tool for understanding the
solution structure of proteins - that stage before crystallography
takes over.
Chapter 1 provides a very basic introduction to the scattering
process, while Chapter 2 explains the theory in detail. Readers
should be forewarned: Chapter 2 provides an in depth overview of
the mathematical background behind the calculation of the radius
of gyration, pair distribution function and even the second virial
coefficient. Chapter 3 provides a detailed discussion of the three
pinhole SAXS camera. The only detectors available then were Geiger
counters and film so the reader must keep in mind that there has
been 55 years of instrument development in the interim.
Nevertheless, the discussion is useful in understanding modern
SAXS cameras. Chapter 4 introduces readers to the interpretation
of results. Chapter 5 compares the SAXS method with other then
state-of-the-art techniques to validate the results from Chapter
4. Chapter 6 goes through a number of applications, with the first
part of the chapter devoted to the study of proteins in dilute
solutions. Finally, an extensive bibliography is provided, that
is obviously only current to 1955.
There are more modern textbooks and reviews on this subject, and
the tools for collecting data and generating results have changed
in the intervening 55 years, but anyone who is seriously
interested in learning about SAXS would benefit from reading this
classic text.
Joseph D. Ferrara, Ph.D.
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