The HD domain, named after the conserved doublet of predicted catalytic
residues, is found in a wide range of bacterial, archaeal and eukaryotic
proteins. It defines a superfamily of phosphohydrolases that can catalyze both
metal-dependent and -independent phosphomonoesterase and phosphodiesterase
reactions for a broad range of substrates [1,2]:
Bacterial polyA polymerases.
Bacterial CCA-adding enzymes, catalyze the addition and repair of the
essential 3'-terminal CCA sequence in tRNAs without using a nucleic acid
The HD-domain proteins appear to be involved in nucleic acid and nucleotide
metabolism, signal transduction and possibly other functions. They are diverse
in terms of both domain architecture and phylogenetic distribution; each of
the completely sequenced genomes encodes more than one version of this domain.
The HD domain is composed of a bundle of α helices with a 5-helix core
(see <PDB:2PAR>). Although all HD domains share key design features, a
striking diversity of catalytic centres have been identified, containing no
metal, mono-, bi- or trinuclear metal binding sites [2,3].
A distinct version of this domain, HD-GYP, contains a number of additional
highly conserved residues. The spectrum of the domains that are associated
with HD-GYP in multidomain proteins suggests that it is probably involved in
signal transduction. The HD-GYP family of HD proteins so far is lacking in
archaea and eukaryotes. The HD-GYP domain is likely to be a conserved scaffold
whose main role is to allow protein-protein interactions with partner GGDEF
domains (see <PDOC50887>) while achieving (a) different function(s) through
diversification of the active-site cavity and the N-terminal regulatory
Xanthomonas campestris RpfG, a multi-phenotype protein involved in
virulence, motility and biofilm regulation. It functions as cyclic di-
3',5'-GMP (c-di-GMP) degrading phosphodiesterase.
Persephonella marina PmGH, a cyclic di-3',5'-GMP (c-di-GMP)
Bdellovibrio bacteriovorus Bd1817, a catalytically inactive protein.
Pseudomonas aeruginosa PA4781 protein, a phosphodiesterase involved in
cyclic di-3',5'-GMP (c-di-GMP) degradation.
Pseudomonas aeruginosa PA4108 protein,
Vibrio cholerae VCA0861, contains tandem HD and HD-GYP domains .
In addition to the HD domain 5-helix core, the HD-GYP domain contains two
extra C-terminal helices (see <PDB:4MCW>) [3,5,7,8].
The HD-related output domain (HDOD) is a protein domain of unknown function.
Proteins containing the HDOD are widespread in diverse bacteria; it can be
present as a stand-alone domain, and also associated with other domains, such
as response regulatory (RR) (see <PDOC50110>), GGDEF (see <PDOC50887>), and
EAL (see <PDOC50883>), suggesting a role in regulation and signaling [9,10]:
Campylobacter jejuni virulence factor CJ048, a stand-alone HDOD containing
protein required for motility and involved in colonization of the chick
Xanthomonas campestris pv. campestris (Xcc) GsmR (general stress and
motility regulator), plays a role in the general stress response of Xcc and
is involved in the expression of genes responsible for flagellum synthesis.
It has a RR domain at the N-terminus and a C-terminal HDOD.
Xanthomonas campestris pv. campestris (Xcc) HdpA, contains a HDOD at the N-
terminus and a GGDEF domain at the C-terminus.
Xu Q., Schwarzenbacher R., McMullan D., Abdubek P., Agarwalla S., Ambing E., Axelrod H., Biorac T., Canaves J.M., Chiu H.-J., Deacon A.M., DiDonato M., Elsliger M.-A., Godzik A., Grittini C., Grzechnik S.K., Hale J., Hampton E., Han G.W., Haugen J., Hornsby M., Jaroszewski L., Klock H.E., Koesema E., Kreusch A., Kuhn P., Lesley S.A., Miller M.D., Moy K., Nigoghossian E., Paulsen J., Quijano K., Reyes R., Rife C., Spraggon G., Stevens R.C., van den Bedem H., Velasquez J., White A., Wolf G., Hodgson K.O., Wooley J., Wilson I.A.
Crystal structure of virulence factor CJ0248 from Campylobacter jejuni at 2.25 A resolution reveals a new fold.
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