Structural highlights
Function
[MOBA_ECOLI] Transfers a GMP moiety from GTP to Mo-molybdopterin (Mo-MPT) cofactor (Moco or molybdenum cofactor) to form Mo-molybdopterin guanine dinucleotide (Mo-MGD) cofactor. Is also involved in the biosynthesis of the bis-MGD form of the Moco cofactor (Mo-bisMGD) in which the metal is symmetrically ligated by the dithiolene groups of two MGD molecules. Is necessary and sufficient for the in vitro activation of the DMSOR molybdoenzyme that uses the Mo-bisMGD form of molybdenum cofactor, which implies formation and efficient insertion of the cofactor into the enzyme without the need of a chaperone. Is specific for GTP since other nucleotides such as ATP and GMP can not be utilized.[1] [2] [3] [4]
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
BACKGROUND: All mononuclear molybdoenzymes bind molybdenum in a complex with an organic cofactor termed molybdopterin (MPT). In many bacteria, including Escherichia coli, molybdopterin can be further modified by attachment of a GMP group to the terminal phosphate of molybdopterin to form molybdopterin guanine dinucleotide (MGD). This modification reaction is required for the functioning of many bacterial molybdoenzymes, including the nitrate reductases, dimethylsulfoxide (DMSO) and trimethylamine-N-oxide (TMAO) reductases, and formate dehydrogenases. The GMP attachment step is catalyzed by the cellular enzyme MobA. RESULTS: The crystal structure of the 21.6 kDa E. coli MobA has been determined by MAD phasing with selenomethionine-substituted protein and subsequently refined at 1. 35 A resolution against native data. The structure consists of a central, predominantly parallel beta sheet sandwiched between two layers of alpha helices and resembles the dinucleotide binding Rossmann fold. One face of the molecule bears a wide depression that is lined by a number of strictly conserved residues, and this feature suggests that this is where substrate binding and catalysis take place. CONCLUSIONS: Through comparisons with a number of structural homologs, we have assigned plausible functions to several of the residues that line the substrate binding pocket. The enzymatic mechanism probably proceeds via a nucleophilic attack by MPT on the GMP donor, most likely GTP, to produce MGD and pyrophosphate. By analogy with related enzymes, this process is likely to require magnesium ions.
Crystal structure of the molybdenum cofactor biosynthesis protein MobA from Escherichia coli at near-atomic resolution.,Stevenson CE, Sargent F, Buchanan G, Palmer T, Lawson DM Structure. 2000 Nov 15;8(11):1115-25. PMID:11080634[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Palmer T, Vasishta A, Whitty PW, Boxer DH. Isolation of protein FA, a product of the mob locus required for molybdenum cofactor biosynthesis in Escherichia coli. Eur J Biochem. 1994 Jun 1;222(2):687-92. PMID:8020507
- ↑ Johnson JL, Indermaur LW, Rajagopalan KV. Molybdenum cofactor biosynthesis in Escherichia coli. Requirement of the chlB gene product for the formation of molybdopterin guanine dinucleotide. J Biol Chem. 1991 Jul 5;266(19):12140-5. PMID:1648082
- ↑ Temple CA, Rajagopalan KV. Mechanism of assembly of the Bis(Molybdopterin guanine dinucleotide)molybdenum cofactor in Rhodobacter sphaeroides dimethyl sulfoxide reductase. J Biol Chem. 2000 Dec 22;275(51):40202-10. PMID:10978348 doi:http://dx.doi.org/10.1074/jbc.M007407200
- ↑ Neumann M, Seduk F, Iobbi-Nivol C, Leimkuhler S. Molybdopterin dinucleotide biosynthesis in Escherichia coli: identification of amino acid residues of molybdopterin dinucleotide transferases that determine specificity for binding of guanine or cytosine nucleotides. J Biol Chem. 2011 Jan 14;286(2):1400-8. doi: 10.1074/jbc.M110.155671. Epub 2010, Nov 16. PMID:21081498 doi:http://dx.doi.org/10.1074/jbc.M110.155671
- ↑ Stevenson CE, Sargent F, Buchanan G, Palmer T, Lawson DM. Crystal structure of the molybdenum cofactor biosynthesis protein MobA from Escherichia coli at near-atomic resolution. Structure. 2000 Nov 15;8(11):1115-25. PMID:11080634
