Multi-wavelength anomalous dispersion
Encyclopedia
Multi-wavelength anomalous diffraction (sometimes Multi-wavelength anomalous dispersion; abbreviated MAD) is a technique used in X-ray crystallography
that facilitates the determination of the three-dimensional structure of biological macromolecules (e.g., DNA, drug receptors) via solution of the phase problem
. This method can be applied in cases where two crystal structures exist -- one structure for which one or more atoms has been replaced by heavy-atoms (in order to cause significant anomalous scattering
from incoming X-rays) and one for which no heavy-atom replacement has been made. The most commonly used heavy atom used for phase determination is selenium: Selenomethionine
is a heavy-atom derivative of the amino acid
methionine
, which can be inserted through the use of selective media during protein expression
. Anomolous diffraction is then recorded at different wavelengths of coherent X-ray light at a synchrotron
facility.
MAD was developed by Wayne Hendrickson
while working as a postdoctoral researcher under Jerome Karle
at the United States Naval Research Laboratory
. The mathematics upon which MAD (and progenitor Single-wavelength Anomalous Diffraction) were based were developed by Jerome Karle
, work for which he was awarded the 1985 Nobel Prize in Chemistry
(along with Herbert Hauptman).
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
that facilitates the determination of the three-dimensional structure of biological macromolecules (e.g., DNA, drug receptors) via solution of the phase problem
Phase problem
In physics the phase problem is the name given to the problem of loss of information concerning the phase that can occur when making a physical measurement. The name itself comes from the field of x-ray crystallography, where the phase problem has to be solved for the determination of a structure...
. This method can be applied in cases where two crystal structures exist -- one structure for which one or more atoms has been replaced by heavy-atoms (in order to cause significant anomalous scattering
Anomalous scattering
In X-ray crystallography, anomalous scattering refers to a change in a diffracting X-ray’s phase that is unique from the rest of the atoms in a crystal due to strong X-ray absorbance . The amount of energy that individual atoms absorb depends on their atomic number...
from incoming X-rays) and one for which no heavy-atom replacement has been made. The most commonly used heavy atom used for phase determination is selenium: Selenomethionine
Selenomethionine
Selenomethionine is an amino acid containing selenium. The L-enantiomer of selenomethionine, known as Se-met and Sem, is a common natural food source of selenium. In vivo, selenomethionine is randomly incorporated instead of methionine and is readily oxidized. Its antioxidant activity arises from...
is a heavy-atom derivative of the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
, which can be inserted through the use of selective media during protein expression
Protein expression
Protein expression is a subcomponent of gene expression. It consists of the stages after DNA has been translated into polypeptide chains, which are ultimately folded into proteins...
. Anomolous diffraction is then recorded at different wavelengths of coherent X-ray light at a synchrotron
Synchrotron
A synchrotron is a particular type of cyclic particle accelerator in which the magnetic field and the electric field are carefully synchronised with the travelling particle beam. The proton synchrotron was originally conceived by Sir Marcus Oliphant...
facility.
MAD was developed by Wayne Hendrickson
Wayne Hendrickson
Wayne A. Hendrickson is an American biophysicist. Hendrickson is also a University professor at Columbia University. Hendrickson is most notably known for innovating the use of multi-wavelength anomalous dispersion as an analytical tool for protein crystallography.Hendrickson obtained a B.A...
while working as a postdoctoral researcher under Jerome Karle
Jerome Karle
Jerome Karle, born Jerome Karfunkel is an American physical chemist. Jointly with Herbert A. Hauptman, he was awarded the Nobel Prize in Chemistry in 1985, for the direct analysis of crystal structures using X-ray scattering techniques.-Early life and education:Karle was born in New York City on...
at the United States Naval Research Laboratory
United States Naval Research Laboratory
The United States Naval Research Laboratory is the corporate research laboratory for the United States Navy and the United States Marine Corps and conducts a program of scientific research and development. NRL opened in 1923 at the instigation of Thomas Edison...
. The mathematics upon which MAD (and progenitor Single-wavelength Anomalous Diffraction) were based were developed by Jerome Karle
Jerome Karle
Jerome Karle, born Jerome Karfunkel is an American physical chemist. Jointly with Herbert A. Hauptman, he was awarded the Nobel Prize in Chemistry in 1985, for the direct analysis of crystal structures using X-ray scattering techniques.-Early life and education:Karle was born in New York City on...
, work for which he was awarded the 1985 Nobel Prize in Chemistry
Nobel Prize in Chemistry
The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...
(along with Herbert Hauptman).
Anomalous Dispersion
- Multi-wavelength Anomalous Dispersion (MAD)
- Single wavelength anomalous dispersionSingle wavelength anomalous dispersionSingle-wavelength anomalous dispersion is a technique used in X-ray crystallography that facilitates the determination of the structure of proteins or other biological macromolecules by allowing the solution of the phase problem. In contrast to multi-wavelength anomalous dispersion, SAD uses a...
(SAD)
Isomorphous Replacement
Two methods for providing the needed phasing information by introducing heavy atoms into isomorphous crystals:- Multiple isomorphous replacementMultiple isomorphous replacementMultiple isomorphous replacement or MIR is the most common approach of solving the phase problem in X-ray crystallography. This method is conducted by soaking the crystal of a sample to be analyzed with a heavy atom solution or co-crystallization with the heavy atom...
(MIR); and - Single isomorphous replacement with anomalous signal (SIRAS)
External links
- MAD phasing — an in depth tutorial with examples, illustrations, and references.
- HHMI Bio for Wayne Hendrickson
- Wayne Hendrickson Home Page
- Hendrickson Laboratory Summary of Research
- Jerome Karl Nobel Biography
- NRL Recognition of Nobel Prize
Computer programs
- The SSRL Absorption Package —
- CHOOCH —
- Shake-and-Bake (SnB) —
- SHELX —