Total 100% <100%
Functional domains 1760 1579 181
UniProtKB 8066 7836 230
GI 11657 11138 519
Structures 4
Reactions 1
Functional domains of this family were last updated on June 10, 2017
New functional domains were last added to this family on Oct. 7, 2014

MoaA requires a companion protein (MoaC) for full biological activity. Together, they are responsible for the formation of Precursor Z from GTP. Recent work by Mehta et al. has deconvoluted the chemistry of these two proteins and they propose that MoaA catalyzes the rearrangement of GTP into a pterin product via a complex rearrangement reaction in which C8 of the purine is inserted between C2' and C3' of the ribose moiety. MoaC then catalyses the intramolecular cyclization reaction of this pterin to precursor Z. Precursor Z is the first precursor involved in the formation of the molybdenum cofactor MoCo. Unlike most nucleoside triphosphate utilising proteins, this reaction is not dependent on Mg(II), and is somewhat inhibited in the presence of Mg(II).

Hänzelmann P, Schindelin H

Binding of 5'-GTP to the C-terminal FeS cluster of the radical S-adenosylmethionine enzyme MoaA provides insights into its mechanism

▸ Abstract

Proc Natl Acad Sci U S A 2006;103(18):6829-6834 | PubMed ID: 16632608

Hänzelmann P, Schindelin H

Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans

▸ Abstract

Proc Natl Acad Sci U S A 2004;101(35):12870-12875 | PubMed ID: 15317939

Hänzelmann P, Schwarz G, Mendel RR

Functionality of alternative splice forms of the first enzymes involved in human molybdenum cofactor biosynthesis

▸ Abstract

J Biol Chem. 2002;277(21):18303-18312 | PubMed ID: 11891227

Hänzelmann P, Hernández HL, Menzel C, García-Serres R, Huynh BH, Johnson MK, Mendel RR, Schindelin H

Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis

▸ Abstract

J Biol Chem. 2004;279(33):34721-34732 | PubMed ID: 15180982

Mehta AP, Hanes JW, Abdelwahed SH, Hilmey DG, Hänzelmann P, Begley TP

Catalysis of a new ribose carbon-insertion reaction by the molybdenum cofactor biosynthetic enzyme MoaA

▸ Abstract

Biochemistry 2013;52(7):1134-1136 | PubMed ID: 23286307

Hover BM, Loksztejn A, Ribeiro AA, Yokoyama K

Identification of a cyclic nucleotide as a cryptic intermediate in molybdenum cofactor biosynthesis

▸ Abstract

J Am Chem Soc 2013;135(18):7019-7032 | PubMed ID: 23627491

Mehta AP, Abdelwahed SH, Xu H, Begley TP

Molybdopterin Biosynthesis: Trapping of intermediates for the MoaA-catalyzed reaction using 2'-deoxyGTP and 2'- chloroGTP as substrate analogs

▸ Abstract

J Am Chem Soc 2014;None(None):None-None | PubMed ID: 24955657

Hover BM, Yokoyama K

C-terminal glycine-gated radical initiation by GTP 3',8-cyclase in the molybdenum cofactor biosynthesis

▸ Abstract

J Am Chem Soc 2015;137(9):3352-3359 | PubMed ID: 25697423

Hover BM, Tonthat NK, Schumacher MA, Yokoyama K

Mechanism of pyranopterin ring formation in molybdenum cofactor biosynthesis

▸ Abstract

Proc Natl Acad Sci U S A 2015;112(20):6347-6352 | PubMed ID: 25941396

No notes.

Static File Downloads

File Name Description Parameters Stats
network.fam276.bs60.mek250K.xgmml One node per sequence network min bit score = 60
max edge count = 250K
size = 131M
num_edges = 250000
num_nodes = 1760
sfld_alignment_fam276.msa Annotated Sequence Alignment, Stockholm format 3 sequences
size: 2.7K

Total number of functional domains in this group.
Number of Functional Domains that have been manually or automatically been assigned to a family.
Number of Functional Domains that have not been assigned to a family.
Number of structures available from the PDB for members of this group.
Number of Functional Domains with 100% of Conserved Residues
Number of Functional Domains with less than 100% Conserved Residues

Active Site

Catalyzed Reaction(s)

cyclic pyranopterin phosphate synthase

+
GTP(4-)
37565
precursor Z(1-)
59648
diphosphate(3-)
33019

EC: 4.1.99.18 | IntEnz: 4.1.99.18 | Kegg: 4.1.99.18 | BioCyc: 4.1.99.18 | BRENDA: 4.1.99.18