MoCF_biosynth

Probable molybdopterin binding domain

• SMART accession number: SM00852
• Description: This domain is found a variety of proteins involved in biosynthesis of molybdopterin cofactor. The domain is presumed to bind molybdopterin. The structure of this domain is known, and it forms an alpha/beta structure. In the known structure of Gephyrin this domain mediates trimerisation.
• Interpro abstract (IPR001453): Eukaryotic and prokaryotic molybdoenzymes require a molybdopterin cofactor (MoCF) for their activity. The biosynthesis of this cofactor involves a complex multistep enzymatic pathway. One of the eukaryotic proteins involved in this pathway is the Drosophila protein cinnamon [(PUBMED:8088525)] which is highly similar to gephyrin, a rat microtubule-associated protein which was thought to anchor the glycine receptor to subsynaptic microtubules.

  Cinnamon and gephyrin are evolutionary related, in their N-terminal half, to the Escherichia coli MoCF biosynthesis proteins mog/chlG and moaB/chlA2 and, in their C-terminal half, to E. coli moeA/chlE.

• GO process: Mo-molybdopterin cofactor biosynthetic process (GO:0006777)

There are 5252 MoCF_biosynth domains in 5120 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: metabolism

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Sola M, Kneussel M, Heck IS, Betz H, Weissenhorn W
• X-ray crystal structure of the trimeric N-terminal domain of gephyrin.
• J Biol Chem. 2001; 276: 25294-301

Gephyrin is a ubiquitously expressed protein that, in the central nervoussystem, forms a submembraneous scaffold for anchoring inhibitoryneurotransmitter receptors in the postsynaptic membrane. The N- andC-terminal domains of gephyrin are homologous to the Escherichia colienzymes MogA and MoeA, respectively, both of which are involved inmolybdenum cofactor biosynthesis. This enzymatic pathway is highlyconserved from bacteria to mammals, as underlined by the ability ofgephyrin to rescue molybdenum cofactor deficiencies in differentorganisms. Here we report the x-ray crystal structure of the N-terminaldomain (amino acids 2-188) of rat gephyrin at 1.9-A resolution.Gephyrin-(2-188) forms trimers in solution, and a sequence motif thoughtto be involved in molybdopterin binding is highly conserved betweengephyrin and the E. coli protein. The atomic structure of gephyrin-(2-188)resembles MogA, albeit with two major differences. The path of theC-terminal ends of gephyrin-(2-188) indicates that the central andC-terminal domains, absent in this structure, should follow a similar3-fold arrangement as the N-terminal region. In addition, a centralbeta-hairpin loop found in MogA is lacking in gephyrin-(2-188). Despitethese differences, both structures show a high degree of surface chargeconservation, which is consistent with their common catalytic function.

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
99.46	map00790	Folate biosynthesis
0.54	map00740	Riboflavin metabolism

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with MoCF_biosynth domain which could be assigned to a KEGG orthologous group, and not all proteins containing MoCF_biosynth domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of MoCF_biosynth domains in PDB

PDB code	Title
1di6	1.45 a crystal structure of the molybdenumm cofactor biosynthesis protein moga from escherichia coli
1di7	1.60 angstrom crystal structure of the molybdenum cofactor biosynthesis protein moga from escherichia coli
1eav	Crystal structures of human gephyrin and plant cnx1 g domains - comparative analysis and functional implications
1fc5	Crystal structure of molybdopterin biosynthesis moea protein
1g8l	Crystal structure of escherichia coli moea
1g8r	Moea
1ihc	X-ray structure of gephyrin n-terminal domain
1jlj	1.6 angstrom crystal structure of the human neuroreceptor anchoring and molybdenum cofactor biosynthesis protein gephyrin
1mkz	Crystal structure of moab protein at 1.6 a resolution.
1o8n	The active site of the molybdenum cofactor biosynthetic protein domain cnx1g
1o8o	The active site of the molybdenum cofactor biosynthetic protein domain cnx1g
1o8q	The active site of the molybdenum cofactor biosenthetic protein domain cnx1g
1r2k	Crystal structure of moab from escherichia coli
1t3e	Structural basis of dynamic glycine receptor clustering
1uux	Structure of a molybdopterin-bound cnx1g domain links molybdenum and copper metabolism
1uuy	Structure of a molybdopterin-bound cnx1g domain links molybdenum and copper metabolism
1uz5	The crystal structure of molybdopterin biosynthesis moea protein from pyrococcus horikosii
1wu2	Crystal structure of molybdopterin biosynthesis moea protein from pyrococcus horikoshii ot3
1xi8	Molybdenum cofactor biosynthesis protein from pyrococcus furiosus pfu-1657500-001
1y5e	Crystal structure of molybdenum cofactor biosynthesis protein b
2f7w	Crystal structure of molybdenum cofactor biosynthesis protein mog from shewanella oneidensis
2f7y	Crystal structure of molybdenum cofactor biosynthesis protein mog from shewanella oneidensis
2fts	Crystal structure of the glycine receptor-gephyrin complex
2fu3	Crystal structure of gephyrin e-domain
2g2c	Putative molybdenum cofactor biosynthesis protein from corynebacterium diphtheriae.
2g4r	Anomalous substructure of moga
2is8	Crystal structure of the molybdopterin biosynthesis enzyme moab (ttha0341) from thermus theromophilus hb8
2nqk	Moea d59n mutant
2nqm	Moea t100a mutant
2nqn	Moea t100w
2nqq	Moea r137q
2nqr	Moea d142n
2nqs	Moea e188a
2nqu	Moea e188q
2nqv	Moea d228a
2nro	Moea k279q
2nrp	Moea r350a
2nrs	Moea s371w
2pbq	Crystal structure of molybdenum cofactor biosynthesis (aq_061) from aquifex aeolicus vf5
2qq1	Crystal structure of molybdenum cofactor biosynthesis (aq_061) other form from aquifex aeolicus vf5
3iwt	Structure of hypothetical molybdenum cofactor biosynthesis protein b from sulfolobus tokodaii
3k6a	Crystal structure of molybdenum cofactor biosynthesis protein mog from shewanella oneidensis

Links (links to other resources describing this domain)

• PFAM: MoCF_biosynth
• INTERPRO: IPR001453