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2o2k

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Revision as of 15:46, 10 September 2015

Crystal Structure of the Activation Domain of Human Methionine Synthase Isoform/Mutant D963E/K1071N

Structural highlights

2o2k is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	MTR (HUMAN)
Activity:	Methionine synthase, with EC number 2.1.1.13
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[METH_HUMAN] Defects in MTR are the cause of methylcobalamin deficiency type G (cblG) [MIM:250940]; also known as homocystinuria-megaloblastic anemia complementation type G. It is an autosomal recessive inherited disease that causes mental retardation, macrocytic anemia, and homocystinuria. Mild deficiency in MS activity could be associated with mild hyperhomocysteinemia, a risk factor for cardiovascular disease and possibly neural tube defects. MS mutations could also be involved in tumorigenesis. Defects in MTR may be a cause of susceptibility to folate-sensitive neural tube defects (FS-NTD) [MIM:601634]. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. Genetic defects in MTR may affect the risk of spina bifida via the maternal rather than the embryonic genotype.^[1] ^[2]

Function

[METH_HUMAN] Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Human methionine synthase (hMS) is a multidomain cobalamin-dependent enzyme that catalyses the conversion of homocysteine to methionine by methyl group transfer. We report here the 1.6 A crystal structure of the C-terminal activation domain of hMS. The structure is C-shaped with the core comprising mixed alpha and beta regions, dominated by a twisted antiparallel beta sheet with a beta-meander region. These features, including the positions of the active-site residues, are similar to the activation domain of Escherichia coli cobalamin-dependent MS (MetH). Structural and solution studies suggest a small proportion of hMS activation domain exists in a dimeric form, which contrasts with the monomeric form of the E. coli homologue. Fluorescence studies show that human activation domain interacts with the FMN-binding domain of human methionine synthase reductase (hMSR). This interaction is enhanced in the presence of S-adenosyl-methionine. Binding of the D963E/K1071N mutant activation domain to the FMN domain of MSR is weaker than with wild-type activation domain. This suggests that one or both of the residues D963 and K1071 are important in partner binding. Key differences in the sequences and structures of hMS and MetH activation domains are recognized and include a major reorientation of an extended 3(10)-containing loop in the human protein. This structural alteration might reflect differences in their respective reactivation complexes and/or potential for dimer formation. The reported structure is a component of the multidomain hMS : MSR complex, and represents an important step in understanding the impact of clinical mutations and polymorphisms in this key electron transfer complex.

Crystal structure and solution characterization of the activation domain of human methionine synthase.,Wolthers KR, Toogood HS, Jowitt TA, Marshall KR, Leys D, Scrutton NS FEBS J. 2007 Feb;274(3):738-50. PMID:17288554^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Doolin MT, Barbaux S, McDonnell M, Hoess K, Whitehead AS, Mitchell LE. Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida. Am J Hum Genet. 2002 Nov;71(5):1222-6. Epub 2002 Oct 9. PMID:12375236 doi:S0002-9297(07)60417-0
↑ O'Leary VB, Mills JL, Pangilinan F, Kirke PN, Cox C, Conley M, Weiler A, Peng K, Shane B, Scott JM, Parle-McDermott A, Molloy AM, Brody LC. Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. Mol Genet Metab. 2005 Jul;85(3):220-7. Epub 2005 Mar 17. PMID:15979034 doi:S1096-7192(05)00052-1
↑ Wolthers KR, Toogood HS, Jowitt TA, Marshall KR, Leys D, Scrutton NS. Crystal structure and solution characterization of the activation domain of human methionine synthase. FEBS J. 2007 Feb;274(3):738-50. PMID:17288554 doi:10.1111/j.1742-4658.2006.05618.x

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2o2k"

@@ Line 2: / Line 2: @@
 <StructureSection load='2o2k' size='340' side='right' caption='[[2o2k]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2o2k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2O2K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2o2k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2O2K FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methionine_synthase Methionine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.13 2.1.1.13] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2o2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o2k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2o2k RCSB], [http://www.ebi.ac.uk/pdbsum/2o2k PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2o2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o2k OCA], [http://pdbe.org/2o2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2o2k RCSB], [http://www.ebi.ac.uk/pdbsum/2o2k PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 29: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2o2k" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Methionine synthase]]
 [[Category: Jowitt, T A]]

2o2k

From Proteopedia

Revision as of 15:46, 10 September 2015

Crystal Structure of the Activation Domain of Human Methionine Synthase Isoform/Mutant D963E/K1071N

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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