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'''Structure of Human ATP:Cobalamin adenosyltransferase bound to ATP.''' | '''Structure of Human ATP:Cobalamin adenosyltransferase bound to ATP.''' | ||
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==Reference== | ==Reference== | ||
Structure of ATP-bound human ATP:cobalamin adenosyltransferase., Schubert HL, Hill CP, Biochemistry. 2006 Dec 26;45(51):15188-96. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17176040 17176040] | Structure of ATP-bound human ATP:cobalamin adenosyltransferase., Schubert HL, Hill CP, Biochemistry. 2006 Dec 26;45(51):15188-96. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17176040 17176040] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Hill, C P.]] | [[Category: Hill, C P.]] | ||
[[Category: Schubert, H L.]] | [[Category: Schubert, H L.]] | ||
[[Category: | [[Category: Adenosyltransferase]] | ||
[[Category: | [[Category: Atp]] | ||
[[Category: | [[Category: Cobalamin]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:23:10 2008'' | |||
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Revision as of 07:23, 4 May 2008
Structure of Human ATP:Cobalamin adenosyltransferase bound to ATP.
OverviewOverview
Mutations in the gene encoding human ATP:cobalamin adenosyltransferase (hATR) can result in the metabolic disorder known as methylmalonic aciduria (MMA). This enzyme catalyzes the final step in the conversion of cyanocobalamin (vitamin B12) to the essential human cofactor adenosylcobalamin. Here we present the 2.5 A crystal structure of ATP bound to hATR refined to an Rfree value of 25.2%. The enzyme forms a tightly associated trimer, where the monomer comprises a five-helix bundle and the active sites lie on the subunit interfaces. Only two of the three active sites within the trimer contain the bound ATP substrate, thereby providing examples of apo- and substrate-bound-active sites within the same crystal structure. Comparison of the empty and occupied sites indicates that twenty residues at the enzyme's N-terminus become ordered upon binding of ATP to form a novel ATP-binding site and an extended cleft that likely binds cobalamin. The structure explains the role of 20 invariant residues; six are involved in ATP binding, including Arg190, which hydrogen bonds to ATP atoms on both sides of the scissile bond. Ten of the hydrogen bonds are required for structural stability, and four are in positions to interact with cobalamin. The structure also reveals how the point mutations that cause MMA are deficient in these functions.
DiseaseDisease
Known disease associated with this structure: Methylmalonic aciduria, vitamin B12-responsive, due to defect in synthesis of adenosylcobalamin, cblB complementation type OMIM:[607568]
About this StructureAbout this Structure
2IDX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structure of ATP-bound human ATP:cobalamin adenosyltransferase., Schubert HL, Hill CP, Biochemistry. 2006 Dec 26;45(51):15188-96. PMID:17176040 Page seeded by OCA on Sun May 4 07:23:10 2008