1s4d
From Proteopedia
Crystal Structure Analysis of the S-adenosyl-L-methionine dependent uroporphyrinogen-III C-methyltransferase SUMT
Structural highlights
FunctionSUMT_SINSX Catalyzes the two successive C-2 and C-7 methylation reactions involved in the conversion of uroporphyrinogen III to precorrin-2 via the intermediate formation of precorrin-1. It is a step in the biosynthesis of both cobalamin (vitamin B12) and siroheme. Neither uroporphyrin III nor the chlorin (factor I) is a substrate of SUMT.[1] 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 PubMedThe crystallographic structure of the Pseudomonas denitrificans S-adenosyl-L-methionine-dependent uroporphyrinogen III methyltransferase (SUMT), which is encoded by the cobA gene, has been solved by molecular replacement to 2.7A resolution. SUMT is a branchpoint enzyme that plays a key role in the biosynthesis of modified tetrapyrroles by controlling flux to compounds such as vitamin B(12) and sirohaem, and catalysing the transformation of uroporphyrinogen III into precorrin-2. The overall topology of the enzyme is similar to that of the SUMT module of sirohaem synthase (CysG) and the cobalt-precorrin-4 methyltransferase CbiF and, as with the latter structures, SUMT has the product S-adenosyl-L-homocysteine bound in the crystal. The roles of a number of residues within the SUMT structure are discussed with respect to their conservation either across the broader family of cobalamin biosynthetic methyltransferases or within the sub-group of SUMT members. The D47N, L49A, F106A, T130A, Y183A and M184A variants of SUMT were generated by mutagenesis of the cobA gene, and tested for SAM binding and enzymatic activity. Of these variants, only D47N and L49A bound the co-substrate S-adenosyl-L-methionine. Consequently, all the mutants were severely restricted in their capacity to synthesise precorrin-2, although both the D47N and L49A variants produced significant quantities of precorrin-1, the monomethylated derivative of uroporphyrinogen III. The activity of these variants is interpreted with respect to the structure of the enzyme. Structure/function studies on a S-adenosyl-L-methionine-dependent uroporphyrinogen III C methyltransferase (SUMT), a key regulatory enzyme of tetrapyrrole biosynthesis.,Vevodova J, Graham RM, Raux E, Schubert HL, Roper DI, Brindley AA, Ian Scott A, Roessner CA, Stamford NP, Elizabeth Stroupe M, Getzoff ED, Warren MJ, Wilson KS J Mol Biol. 2004 Nov 19;344(2):419-33. PMID:15522295[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Large Structures | Brindley AA | Getzoff ED | Graham RM | Raux E | Roessner CA | Roper DI | Schubert HL | Scott AI | Stamford NPJ | Stroupe ME | Vevodova J | Warren MJ | Wilson KS
