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[[Image:1n7m.gif|left|200px]]
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{{STRUCTURE_1n7m|  PDB=1n7m  |  SCENE=  }}
'''Germline 7G12 with N-methylmesoporphyrin'''


==Germline 7G12 with N-methylmesoporphyrin==
<StructureSection load='1n7m' size='340' side='right'caption='[[1n7m]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1n7m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N7M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N7M FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MMP:N-METHYLMESOPORPHYRIN'>MMP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1n7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n7m OCA], [https://pdbe.org/1n7m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n7m RCSB], [https://www.ebi.ac.uk/pdbsum/1n7m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n7m ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[https://omim.org/entry/254500 254500]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4.
== Function ==
[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n7/1n7m_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1n7m ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The crystal structure of the Michaelis complex between the Fab fragment of ferrochelatase antibody 7G12 and its substrate mesoporphyrin has been solved to 2.6-A resolution. The antibody-bound mesoporphyrin clearly adopts a nonplanar conformation and reveals that the antibody catalyzes the porphyrin metallation reaction by straining/distorting the bound substrate toward the transition-state configuration. The crystal structures of the Fab fragment of the germ-line precursor antibody to 7G12 and its complex with the hapten N-methylmesoporphyrin have also been solved. A comparison of these structures with the corresponding structures of the affinity-matured antibody 7G12 reveals the molecular mechanism by which the immune system evolves binding energy to catalyze this reaction.


==Overview==
Structural evidence for substrate strain in antibody catalysis.,Yin J, Andryski SE, Beuscher AE 4th, Stevens RC, Schultz PG Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):856-61. Epub 2003 Jan 24. PMID:12552112<ref>PMID:12552112</ref>
The crystal structure of the Michaelis complex between the Fab fragment of ferrochelatase antibody 7G12 and its substrate mesoporphyrin has been solved to 2.6-A resolution. The antibody-bound mesoporphyrin clearly adopts a nonplanar conformation and reveals that the antibody catalyzes the porphyrin metallation reaction by straining/distorting the bound substrate toward the transition-state configuration. The crystal structures of the Fab fragment of the germ-line precursor antibody to 7G12 and its complex with the hapten N-methylmesoporphyrin have also been solved. A comparison of these structures with the corresponding structures of the affinity-matured antibody 7G12 reveals the molecular mechanism by which the immune system evolves binding energy to catalyze this reaction.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1N7M is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus,_homo_sapiens Mus musculus, homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N7M OCA].
</div>
<div class="pdbe-citations 1n7m" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structural evidence for substrate strain in antibody catalysis., Yin J, Andryski SE, Beuscher AE 4th, Stevens RC, Schultz PG, Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):856-61. Epub 2003 Jan 24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12552112 12552112]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
[[Category: Mus musculus, homo sapiens]]
== References ==
[[Category: Single protein]]
<references/>
[[Category: Andryski, S E.]]
__TOC__
[[Category: IV, A E.Beuscher.]]
</StructureSection>
[[Category: Schultz, P G.]]
[[Category: Homo sapiens]]
[[Category: Stevens, R C.]]
[[Category: Large Structures]]
[[Category: Yin, J.]]
[[Category: Mus musculus]]
[[Category: Immune system]]
[[Category: Andryski SE]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 02:11:38 2008''
[[Category: Beuscher IV AE]]
[[Category: Schultz PG]]
[[Category: Stevens RC]]
[[Category: Yin J]]

Latest revision as of 07:03, 30 October 2024

Germline 7G12 with N-methylmesoporphyrin

1n7m, resolution 1.80Å

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