Histidine 90 Function in 4-Chlorobenzoyl-Coenzyme A Dehalogenase Catalysis

Zhang, Wenhai; Wei, Yansheng; Luo, Liang; Taylor, Katherine A.; Yang, Guang; Dunaway‐Mariano, Debra; Benning, Matthew M.; Holden, Hazel M.

doi:10.1021/bi0251743

Cited by 9 publications

(18 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this case, the rate-limiting transition state might be associated with the second partial reaction, the hydrolysis of the aspartylphosphate intermediate. The contribution of Asp-10 is consistent with the rate contribution of a general base to the rate of hydrolysis of a covalent enzyme ester intermediate (31). Thus, we conclude that the Asp-10 contributes to the trigonal-bipyramidal mold that frames the transition states of both partial reactions, and that this contribution is most pronounced in the stabilization of the transition state of the first partial reaction.…”

Section: The Asp؉2 Residue Asp-10 Is An Essential Component Of the Hadsfsupporting

confidence: 75%

The catalytic scaffold of the haloalkanoic acid dehalogenase enzyme superfamily acts as a mold for the trigonal bipyramidal transition state

Dunaway‐Mariano

Allen

2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

The evolution of new catalytic activities and specificities within an enzyme superfamily requires the exploration of sequence space for adaptation to a new substrate with retention of those elements required to stabilize key intermediates/transition states. Here, we propose that core residues in the large enzyme family, the haloalkanoic acid dehalogenase enzyme superfamily (HADSF) form a ''mold'' in which the trigonal bipyramidal transition states formed during phosphoryl transfer are stabilized by electrostatic forces. The vanadate complex of the hexose phosphate phosphatase BT4131 from Bacteroides thetaiotaomicron VPI-5482 (HPP) determined at 1.00 Å resolution via X-ray crystallography assumes a trigonal bipyramidal coordination geometry with the nucleophilic Asp-8 and one oxygen ligand at the apical position. Remarkably, the tungstate in the complex determined to 1.03 Å resolution assumes the same coordination geometry. The contribution of the general acid/base residue Asp-10 in the stabilization of the trigonal bipyramidal species via hydrogen-bond formation with the apical oxygen atom is evidenced by the 1.52 Å structure of the D10A mutant bound to vanadate. This structure shows a collapse of the trigonal bipyramidal geometry with displacement of the water molecule formerly occupying the apical position. Furthermore, the 1.07 Å resolution structure of the D10A mutant complexed with tungstate shows the tungstate to be in a typical ''phosphate-like'' tetrahedral configuration. The analysis of 12 liganded HADSF structures deposited in the protein data bank (PDB) identified stringently conserved elements that stabilize the trigonal bipyramidal transition states by engaging in favorable electrostatic interactions with the axial and equatorial atoms of the transferring phosphoryl group.phosphatase ͉ phosphoryl transfer ͉ transition state stabilization ͉ trigonal bipyramidal phosphorane

show abstract

Section: The Asp؉2 Residue Asp-10 Is An Essential Component Of the Hadsfsupporting

confidence: 75%

The catalytic scaffold of the haloalkanoic acid dehalogenase enzyme superfamily acts as a mold for the trigonal bipyramidal transition state

Dunaway‐Mariano

Allen

2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The compound is first activated by conjugation to coenzyme A, after which a hydrolytic dehalogenase (CbzA) that belongs to the enoyl hydratase superfamily, displaces the halogen by a nucleophilic addition‐elimination mechanism. No distinct halide‐binding site is present in the X‐ray structure, but a nucleophilic aspartate and a histidine involved in catalysis were identified (Zhang et al ., 2001). Another aromatic dehalogenase is tetrachlorohydroquinone dehalogenase.…”

Section: Dehalogenase Mechanismsmentioning

confidence: 99%

Bacterial degradation of xenobiotic compounds: evolution and distribution of novel enzyme activities

Janssen

Dinkla

Poelarends

et al. 2005

Environmental Microbiology

226

142

View full text Add to dashboard Cite

SummaryBacterial dehalogenases catalyse the cleavage of carbon-halogen bonds, which is a key step in aerobic mineralization pathways of many halogenated compounds that occur as environmental pollutants. There is a broad range of dehalogenases, which can be classified in different protein superfamilies and have fundamentally different catalytic mechanisms. Identical dehalogenases have repeatedly been detected in organisms that were isolated at different geographical locations, indicating that only a restricted number of sequences are used for a certain dehalogenation reaction in organohalogen-utilizing organisms. At the same time, massive random sequencing of environmental DNA, and microbial genome sequencing projects have shown that there is a large diversity of dehalogenase sequences that is not employed by known catabolic pathways. The corresponding proteins may have novel functions and selectivities that could be valuable for biotransformations in the future. Apparently, traditional enrichment and metagenome approaches explore different segments of sequence space. This is also observed with alkane hydroxylases, a category of proteins that can be detected on basis of conserved sequence motifs and for which a large number of sequences has been found in isolated bacterial cultures and genomic databases. It is likely that ongoing genetic adaptation, with the recruitment of silent sequences into functional catabolic routes and evolution of substrate range by mutations in structural genes, will further enhance the catabolic potential of bacteria toward synthetic organohalogens and ultimately contribute to cleansing the environment of these toxic and recalcitrant chemicals.

show abstract

“…For molecular replacement, a homology model was built using MODELLER (Såli and Blundell 1993), derived from the coordinates of three proteins of known structure that exhibited highest sequence homology with the mature rat mECI sequence. A FASTA search (Pearson and Lipman 1988) through the PDB database (Berman et al 2000) showed AUH protein (Kurimoto et al 2001; PDB accession code 1HZD), crotonase (Bahnson et al 2002; PDB accession code 1EY3), and 4‐chlorobenzoyl‐ CoA dehalogenase (Zhang et al 2001; PDB accession code 1JXZ) to have 29%, 23%, and 24% sequence identities, respectively. Since the Matthews coefficient suggested one molecule per asymmetric unit (V M =3.44), the homology model, corresponding to one monomer, was used as a probe for crossrotational molecular replacement.…”

Section: Methodsmentioning

confidence: 99%

Domain swapping in the low‐similarity isomerase/hydratase superfamily: The crystal structure of rat mitochondrial Δ³, Δ²‐enoyl‐CoA isomerase

Hubbard

Schulz

et al. 2005

Protein Science

View full text Add to dashboard Cite

Two monofunctional D 3 ,D 2 -enoyl-CoA isomerases, one in mitochondria (mECI) and the other in both mitochondria and peroxisomes (pECI), belong to the low-similarity isomerase/hydratase superfamily. Both enzymes catalyze the movement of a double bond from C3 to C2 of an unsaturated acyl-CoA substrate for re-entry into the b-oxidation pathway. Mutagenesis has shown that Glu165 of rat mECI is involved in catalysis; however, the putative catalytic residue in yeast pECI, Glu158, is not conserved in mECI. To elucidate whether Glu165 of mECI is correctly positioned for catalysis, the crystal structure of rat mECI has been solved. Crystal packing suggests the enzyme is trimeric, in contrast to other members of the superfamily, which appear crystallographically to be dimers of trimers. The polypeptide fold of mECI, like pECI, belongs to a subset of this superfamily in which the C-terminal domain of a given monomer interacts with its own N-terminal domain. This differs from that of crotonase and 1,4-dihydroxy-2-naphtoyl-CoA synthase, whose C-terminal domains are involved in domain swapping with an adjacent monomer. The structure confirms Glu165 as the putative catalytic acid/base, positioned to abstract the pro-R proton from C2 and reprotonate at C4 of the acyl chain. The large tunnel-shaped active site cavity observed in the mECI structure explains the relative substrate promiscuity in acyl-chain length and stereochemistry. Comparison with the crystal structure of pECI suggests the catalytic residues from both enzymes are spatially conserved but not in their primary structures, providing a powerful reminder of how catalytic residues cannot be determined solely by sequence alignments.Keywords: domain swapping; low-similarity isomerase/hydratase superfamily; enoyl-CoA isomerase; crystal structure; fatty acid metabolism To metabolize unsaturated fatty acids, eukaryotes require two auxiliary enzymes, 2,4-dienoyl-CoA reductase (DCR) and D 3,D 2 -enoyl-CoA isomerase (ECI; EC 5.3.3.8). ECI catalyzes the movement of the double bond between carbons 3 and 4 of the acyl chain to carbons 2 and 3, allowing the acyl-CoA to re-enter the b-oxidation pathway at the second step. ECI differs from DCR in that it is essential for the metabolism of all fatty acids with double bonds at odd as well as even carbon positions (Schulz and Kunau 1987). However, like DCR, ECI is relatively promiscuous, catalyzing the isomerization of both cis and trans unsaturated fatty acyl chains (Stoffel et al. 1964;Palosaari et al. 1990;Zhang et al. 2002) (Palosaari et al. 1990;Zhang et al. 2002), as well as in the peroxisomes of yeast (Geisbrecht et al. 1998;Gurvitz et al. 1998). Sequence analysis shows they belong to the low-similarity isomerase/hydratase superfamily (LSI/H) (Muller-Newen et al. 1995;Holden et al. 2001), with the mammalian forms grouped into four classes based on their substrate specificity, organelle location, and physical composition: mitochondrial enoyl-CoA isomerase (mECI), mitochondrial enoyl-CoA hydratase 1 (crotonase), peroxisom...

show abstract

Histidine 90 Function in 4-Chlorobenzoyl-Coenzyme A Dehalogenase Catalysis

Cited by 9 publications

References 0 publications

The catalytic scaffold of the haloalkanoic acid dehalogenase enzyme superfamily acts as a mold for the trigonal bipyramidal transition state

The catalytic scaffold of the haloalkanoic acid dehalogenase enzyme superfamily acts as a mold for the trigonal bipyramidal transition state

Bacterial degradation of xenobiotic compounds: evolution and distribution of novel enzyme activities

Domain swapping in the low‐similarity isomerase/hydratase superfamily: The crystal structure of rat mitochondrial Δ³, Δ²‐enoyl‐CoA isomerase

Contact Info

Product

Resources

About

Histidine 90 Function in 4-Chlorobenzoyl-Coenzyme A Dehalogenase Catalysis

Cited by 9 publications

References 0 publications

The catalytic scaffold of the haloalkanoic acid dehalogenase enzyme superfamily acts as a mold for the trigonal bipyramidal transition state

The catalytic scaffold of the haloalkanoic acid dehalogenase enzyme superfamily acts as a mold for the trigonal bipyramidal transition state

Bacterial degradation of xenobiotic compounds: evolution and distribution of novel enzyme activities

Domain swapping in the low‐similarity isomerase/hydratase superfamily: The crystal structure of rat mitochondrial Δ3, Δ2‐enoyl‐CoA isomerase

Contact Info

Product

Resources

About

Domain swapping in the low‐similarity isomerase/hydratase superfamily: The crystal structure of rat mitochondrial Δ³, Δ²‐enoyl‐CoA isomerase