Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sequencing of all human immunoglobulin (Ig) germline gene segments has recently been completed. However, our first glimpses of the recombined products of this combinatorial gene system were in the 1970s, in landmark publications, reporting the crystal structures of two human myeloma proteins, the Mcg lambda light chain dimer and the New IgG1(lambda) Fab. Although numerous crystal structures of murine and human antibodies have now been determined, only a relatively small proportion of the human germline genes have had their corresponding protein three-dimensional structures resolved. Therefore, further structural investigations are required before the inherent diversity of the antibody repertoire can be fully appreciated. We discuss the detailed structural information available for human antibodies with regard to their immune functions. Also discussed, is how the structural information is finding application in the 'humanization' of murine antibodies as part of their development as 'biopharmaceuticals' for the treatment of human disease.
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PMID:Crystal structures of human antibodies: a detailed and unfinished tapestry of immunoglobulin gene products. 1244 1

The lambda-type light chain dimer from a patient (Mcg) with multiple myeloma and amyloidosis was a pioneer protein for determining the three-dimensional structures of immunoglobulins, understanding the effects of ligand binding, and exploring the use of combinatorial methods to identify novel peptides complementary to protein active sites. Despite 30 years of intense study, there are still unanswered questions about the structure of the Mcg dimer, especially with respect to positions of hydrogen atoms and solvent molecules. In the present report, we describe two techniques that will help define the roles of solvent in ligand interactions and complex formation with this immunoglobulin fragment: (1) introduction of helium as a cryogenic agent during X-ray data collection; and (2) addition of neutron diffraction analyses. These techniques should provide improved resolution, and a more accurate structure of the Mcg dimer. Resolution enhancements of 0.5 A have been achieved in preliminary experiments with cryogenic helium, as compared with the best X-ray diffraction data obtained previously. In the near future, neutron diffraction studies should produce the first hydrogen structure for the Mcg dimer and help elucidate the ligand preferences and amyloidogenic properties of this eminently useful protein.
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PMID:Mcg in 2030: new techniques for atomic position determination of immune complexes. 1244 7


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