Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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MR_MLE Mandelate racemase / muconate lactonizing enzyme, C-terminal domain

SMART accession number:	SM00922
Description:	Mandelate racemase (MR) and muconate lactonizing enzyme (MLE) are two bacterial enzymes involved in aromatic acid catabolism. They catalyze mechanistically distinct reactions yet they are related at the level of their primary, quaternary (homooctamer) and tertiary structures (PUBMED:2215699), (PUBMED:8256284). This entry represents the C-terminal region of these proteins.
Interpro abstract (IPR013342):	Mandelate racemase EC 5.1.2.2 (MR) and muconate lactonising enzyme EC 5.5.1.1 (MLE) are two bacterial enzymes involved in aromatic acid catabolism. They catalyse mechanistically distinct reactions yet they are related at the level of their primary, quaternary (homooctamer) and tertiary structures [(PUBMED:2215699), (PUBMED:8256284)]. A number of other proteins also seem to be evolutionary related to these two enzymes. These include, various plasmid-encoded chloromuconate cycloisomerases EC 5.5.1.7, Escherichia coli protein rspA [(PUBMED:7545940)], E. coli bifunctional DGOA protein, E. coli hypothetical proteins ycjG, yfaW and yidU and a hypothetical protein from Streptomyces ambofaciens [(PUBMED:8277241)]. This entry represents the C-terminal region of these proteins.
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 3781 MR_MLE domains in 3781 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a MR_MLE domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with MR_MLE domain is also avaliable.

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  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Homo sapiens, Takifugu rubripes

• 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.

  • Petsko GA, Kenyon GL, Gerlt JA, Ringe D, Kozarich JW
  • On the origin of enzymatic species.
  • Trends Biochem Sci. 1993; 18: 372-6
  • Display abstract

  • The diversity of enzyme catalytic function is remarkable, particularlywhen one considers that ancestral life forms must have started with a muchsmaller ensemble of proteins. In this article, we discuss the evolution ofthe mandelate pathway in pseudomonads as an example of how catalyticdiversity may have evolved. We suggest that existing enzymes that catalysethe chemistry needed to accomplish a transformation were recruited,followed by the evolution of specific binding.

  • Neidhart DJ, Kenyon GL, Gerlt JA, Petsko GA
  • Mandelate racemase and muconate lactonizing enzyme are mechanisticallydistinct and structurally homologous.
  • Nature. 1990; 347: 692-4
  • Display abstract

  • Mandelate racemase (MR) and muconate lactonizing enzyme (MLE) catalyseseparate and mechanistically distinct reactions necessary for thecatabolism of aromatic acids by Pseudomonas putida. The X-ray crystalstructure of MR, solved at 2.5 A resolution, reveals that the secondary,tertiary and quaternary structures of MR and MLE are remarkably similar;also, MR and MLE are about 26% identical in primary structure. However, MRhas no detectable MLE activity and vice versa. Thus, MR and MLE constitutethe first example of enzymes that catalyse different reactions, as opposedto mechanistically identical reactions on different substrates, yetpossess sufficient structural and sequence identity that they are likelyto have evolved from a common ancestor. The discovery that MR and MLEcatalyse different reactions but share a common structural framework hasbroad implications for the natural evolution of enzymes and metabolicpathways, as well as for the rational modification of enzyme activities.

  • Goldman A, Ollis DL, Steitz TA
  • Crystal structure of muconate lactonizing enzyme at 3 A resolution.
  • J Mol Biol. 1987; 194: 143-53
  • Display abstract

  • The crystal structure of muconate lactonizing enzyme has been solved at 3A resolution, and an unambiguous alpha-carbon backbone chain trace made.The enzyme contains three domains; the central domain is aparallel-stranded alpha-beta barrel, which has previously been reported insix other enzymes, including triose phosphate isomerase and pyruvatekinase. One novel feature of this enzyme is that its alpha-beta barrel hasonly seven parallel alpha-helices around the central core of eightparallel beta-strands; all other known alpha-beta barrels contain eightsuch helices. The N-terminal (alpha + beta) and C-terminal domains coverthe cleft where the eighth helix would be. The active site of muconatelactonizing enzyme has been found by locating the manganese ion that isessential for catalytic activity, and by binding and locating aninhibitor, alpha-ketoglutarate. The active site lies in a cleft betweenthe N-terminal and barrel domains; when the active sites of muconatelactonizing enzyme and triose phosphate isomerase are superimposed,barrel-strand 1 of triose phosphate isomerase is aligned withbarrel-strand 3 of muconate lactonizing enzyme. This implies thatstructurally homologous active-site residues in the two enzymes arecarried on different parts of the primary sequence; the ancestral genewould had to have been transposed during its evolution to the modernproteins, which seems unlikely. Therefore, these two enzymes may berelated by convergent, rather than divergent, evolution.

• Structure (3D structures containing this domain)

• 3D Structures of MR_MLE domains in PDB

  PDB code	Main view	Title
  1bkh		Muconate lactonizing enzyme from pseudomonas putida
  1bqg		The structure of the d-glucarate dehydratase protein from pseudomonas putida
  1dtn		Mandelate racemase mutant d270n co-crystallized with (s)- atrolactate
  1ec7		E. coli glucarate dehydratase native enzyme
  1ec8		E. coli glucarate dehydratase bound to product 2,3- dihydroxy-5-oxo-hexanedioate
  1ec9		E. coli glucarate dehydratase bound to xylarohydroxamate
  1ecq		E. coli glucarate dehydratase bound to 4-deoxyglucarate
  1f9c		Crystal structure of mle d178n variant
  1fhu		Crystal structure analysis of o-succinylbenzoate synthase from e. coli
  1fhv		Crystal structure analysis of o-succinylbenzoate synthase from e. coli complexed with mg and osb
  1jct		Glucarate dehydratase, n341l mutant orthorhombic form
  1jdf		Glucarate dehydratase from e.coli n341d mutant
  1jpd		L-ala-d/l-glu epimerase
  1jpm		L-ala-d/l-glu epimerase
  1mdl		Mandelate racemase mutant k166r co-crystallized with (r)- mandelate
  1mdr		The role of lysine 166 in the mechanism of mandelate racemase from pseudomonas putida: mechanistic and crystallographic evidence for stereospecific alkylation by (r)-alpha-phenylglycidate
  1mns		On the role of lysine 166 in the mechanism of mandelate racemase from pseudomonas putida: mechanistic and crystallographic evidence for stereospecific alkylation by (r)-alpha-phenylglycidate
  1mra		Mandelate racemase mutant d270n co-crystallized with (s)- atrolactate
  1muc		Structure of muconate lactonizing enzyme at 1.85 angstroms resolution
  1nu5		Crystal structure of pseudomonas sp. p51 chloromuconate lactonizing enzyme
  1r0m		Structure of deinococcus radiodurans n-acylamino acid racemase at 1.3 : insights into a flexible binding pocket and evolution of enzymatic activity
  1r6w		Crystal structure of the k133r mutant of o-succinylbenzoate synthase (osbs) from escherichia coli. complex with shchc
  1rvk		Crystal structure of enolase agr_l_2751 from agrobacterium tumefaciens
  1sja		X-ray structure of o-succinylbenzoate synthase complexed with n-acetylmethionine
  1sjb		X-ray structure of o-succinylbenzoate synthase complexed with o-succinylbenzoic acid
  1sjc		X-ray structure of o-succinylbenzoate synthase complexed with n-succinyl methionine
  1sjd		X-ray structure of o-succinylbenzoate synthase complexed with n-succinyl phenylglycine
  1tkk		The structure of a substrate-liganded complex of the l-ala- d/l-glu epimerase from bacillus subtilis
  1tzz		Crystal structure of the protein l1841, unknown member of enolase superfamily from bradyrhizobium japonicum
  1wue		Crystal structure of protein gi:29375081, unknown member of enolase superfamily from enterococcus faecalis v583
  1wuf		Crystal structure of protein gi:16801725, member of enolase superfamily from listeria innocua clip11262
  1xpy		Structural basis for catalytic racemization and substrate specificity of an n-acylamino acid racemase homologue from deinococcus radiodurans
  1xs2		Structural basis for catalytic racemization and substrate specificity of an n-acylamino acid racemase homologue from deinococcus radiodurans
  1yey		Crystal structure of l-fuconate dehydratase from xanthomonas campestris pv. campestris str. atcc 33913
  2chr		A re-evaluation of the crystal structure of chloromuconate cycloisomerase
  2dw6		Crystal structure of the mutant k184a of d-tartrate dehydratase from bradyrhizobium japonicum complexed with mg++ and d-tartrate
  2dw7		Crystal structure of d-tartrate dehydratase from bradyrhizobium japonicum complexed with mg++ and meso- tartrate
  2fkp		The mutant g127c-t313c of deinococcus radiodurans n- acylamino acid racemase
  2gdq		Crystal structure of mandelate racemase/muconate lactonizing enzyme from bacillus subtilis at 1.8 a resolution
  2gge		Crystal structure of mandelate racemase/muconate lactonizing enzyme from bacillus subtilis complexed with mg++ at 1.8 a
  2ggg		The mutant a68c-d72c of deinococcus radiodurans n-acylamino acid racemase
  2ggh		The mutant a68c-d72c-nlq of deinococcus radiodurans nacylamino acid racemase
  2ggi		The mutant e149c-a182c of deinococcus radiodurans n- acylamino acid racemase
  2ggj		The mutant y218c of deinococcus radiodurans n-acylamino acid racemase
  2gl5		Crystal structure of putative dehydratase from salmonella thyphimurium
  2gsh		Crystal structure of l-rhamnonate dehydratase from salmonella typhimurium
  2hne		Crystal structure of l-fuconate dehydratase from xanthomonas campestris pv. campestris str. atcc 33913
  2hxt		Crystal structure of l-fuconate dehydratase from xanthomonas campestris liganded with mg++ and d- erythronohydroxamate
  2hxu		Crystal structure of k220a mutant of l-fuconate dehydratase from xanthomonas campestris liganded with mg++ and l- fuconate
  2hzg		Crystal stucture of predicted mandelate racemase from rhodobacter sphaeroides
  2i5q		Crystal structure of apo l-rhamnonate dehydratase from escherichia coli
  2mnr		Mechanism of the reaction catalyzed by mandelate racemase. 2. crystal structure of mandelate racemase at 2.5 angstroms resolution: identification of the active site and possible catalytic residues
  2muc		Muconate cycloisomerase variant f329i
  2nql		Crystal structure of a member of the enolase superfamily from agrobacterium tumefaciens
  2o56		Crystal structure of a member of the enolase superfamily from salmonella typhimurium
  2ofj		Crystal structure of the e190a mutant of o-succinylbenzoate synthase from escherichia coli
  2og9		Crystal structure of mandelate racemase/muconate lactonizing enzyme from polaromonas sp. js666
  2oo6		Crystal structure of putative l-alanine-dl-glutamate epimerase from burkholderia xenovorans strain lb400
  2opj		Crystal structure of o-succinylbenzoate synthase
  2oqh		Crystal structure of an isomerase from streptomyces coelicolor a3(2)
  2oqy		The crystal structure of muconate cycloisomerase from oceanobacillus iheyensis
  2ovl		Crystal structure of a racemase from streptomyces coelicolor a3(2)
  2ox4		Crystal structure of putative dehydratase from zymomonas mobilis zm4
  2oz3		Crystal structure of l-rhamnonate dehydratase from azotobacter vinelandii
  2oz8		Crystal structure of putative mandelate racemase from mesorhizobium loti
  2ozt		Crystal structure of o-succinylbenzoate synthase from thermosynechococcus elongatus bp-1
  2p0i		Crystal structure of l-rhamnonate dehydratase from gibberella zeae
  2p3z		Crystal structure of l-rhamnonate dehydratase from salmonella typhimurium
  2p88		Crystal structure of n-succinyl arg/lys racemase from bacillus cereus atcc 14579
  2p8b		Crystal structure of n-succinyl arg/lys racemase from bacillus cereus atcc 14579 complexed with n-succinyl lys.
  2p8c		Crystal structure of n-succinyl arg/lys racemase from bacillus cereus atcc 14579 complexed with n-succinyl arg.
  2pge		Crystal structure of menc from desulfotalea psychrophila lsv54
  2pgw		Crystal structure of a putative muconate cycloisomerase from sinorhizobium meliloti 1021
  2pmq		Crystal structure of a mandelate racemase/muconate lactonizing enzyme from roseovarius sp. htcc2601
  2pod		Crystal structure of a member of enolase superfamily from burkholderia pseudomallei k96243
  2poz		Crystal structure of a putative dehydratase from mesorhizobium loti
  2pp0		Crystal structure of l-talarate/galactarate dehydratase from salmonella typhimurium lt2
  2pp1		Crystal structure of l-talarate/galactarate dehydratase from salmonella typhimurium lt2 liganded with mg and l- lyxarohydroxamate
  2pp3		Crystal structure of l-talarate/galactarate dehydratase mutant k197a liganded with mg and l-glucarate
  2ppg		Crystal structure of putative isomerase from sinorhizobium meliloti
  2ps2		Crystal structure of putative mandelate racemase/muconate lactonizing enzyme from aspergillus oryzae
  2qdd		Crystal structure of a member of enolase superfamily from roseovarius nubinhibens ism
  2qde		Crystal structure of mandelate racemase/muconate lactonizing family protein from azoarcus sp. ebn1
  2qjj		Crystal structure of d-mannonate dehydratase from novosphingobium aromaticivorans
  2qjm		Crystal structure of the k271e mutant of mannonate dehydratase from novosphingobium aromaticivorans complexed with mg and d-mannonate
  2qjn		Crystal structure of d-mannonate dehydratase from novosphingobium aromaticivorans complexed with mg and 2- keto-3-deoxy-d-gluconate
  2qq6		Crystal structure of mandelate racemase/muconate lactonizing enzyme-like protein from rubrobacter xylanophilus dsm 9941
  2qvh		Crystal structure of o-succinylbenzoate synthase complexed with o-succinyl benzoate (osb)
  2rdx		Crystal structure of mandelate racemase/muconate lactonizing enzyme from roseovarius nubinhibens ism
  2zad		Crystal structure of muconate cycloisomerase from thermotoga maritima msb8
  2zc8		Crystal structure of n-acylamino acid racemase from thermus thermophilus hb8
  3bjs		Crystal structure of a member of enolase superfamily from polaromonas sp. js666
  3box		Crystal structure of l-rhamnonate dehydratase from salmonella typhimurium complexed with mg
  3bsm		Crystal structure of d-mannonate dehydratase from chromohalobacter salexigens
  3cb3		Crystal structure of l-talarate dehydratase from polaromonas sp. js666 complexed with mg and l-glucarate
  3ck5		Crystal structure of a racemase from streptomyces coelicolor a3(2) with bound magnesium
  3ct2		Crystal structure of muconate cycloisomerase from pseudomonas fluorescens
  3cxo		Crystal structure of l-rhamnonate dehydratase from salmonella typhimurium complexed with mg and 3-deoxy-l- rhamnonate
  3cyj		Crystal structure of a mandelate racemase/muconate lactonizing enzyme-like protein from rubrobacter xylanophilus
  3d46		Crystal structure of l-rhamnonate dehydratase from salmonella typhimurium complexed with mg and l-tartrate
  3d47		Crystal structure of l-rhamnonate dehydratase from salmonella typhimurium complexed with mg and d-malate
  3ddm		Crystal structure of mandelate racemase/muconate lactonizing enzyme from bordetella bronchiseptica rb50
  3deq		Crystal structure of dipeptide epimerase from thermotoga maritima complexed with l-ala-l-leu dipeptide
  3der		Crystal structure of dipeptide epimerase from thermotoga maritima complexed with l-ala-l-lys dipeptide
  3des		Crystal structure of dipeptide epimerase from thermotoga maritima complexed with l-ala-l-phe dipeptide
  3dfh		Crystal structure of putative mandelate racemase / muconate lactonizing enzyme from vibrionales bacterium swat-3
  3dfy		Crystal structure of apo dipeptide epimerase from thermotoga maritima
  3dg3		Crystal structure of muconate lactonizing enzyme from mucobacterium smegmatis
  3dg6		Crystal structure of muconate lactonizing enzyme from mucobacterium smegmatis complexed with muconolactone
  3dg7		Crystal structure of muconate lactonizing enzyme from mucobacterium smegmatis complexed with muconolactone
  3dgb		Crystal structure of muconate lactonizing enzyme from pseudomonas fluorescens complexed with muconolactone
  3dip		Crystal structure of an enolase protein from the environmental genome shotgun sequencing of the sargasso sea
  3eez		Crystal structure of a putative mandelate racemase/muconate lactonizing enzyme from silicibacter pomeroyi
  3ekg		Crystal structure of l-rhamnonate dehydratase from azotobacter vinelandii complexed with mg and l-tartrate
  3es7		Crystal structure of divergent enolase from oceanobacillus iheyensis complexed with mg and l-malate.
  3es8		Crystal structure of divergent enolase from oceanobacillus iheyensis complexed with mg and l-malate.
  3fcp		Crystal structure of muconate lactonizing enzyme from klebsiella pneumoniae
  3fj4		Crystal structure of muconate lactonizing enzyme from pseudomonas fluorescens complexed with muconolactone
  3fvd		Crystal structure of a member of enolase superfamily from roseovarius nubinhibens ism complexed with magnesium
  3fxg		Crystal structure of rhamnonate dehydratase from gibberella zeae complexed with mg
  3fyy		Crystal structure of divergent enolase from oceanobacillus iheyensis complexed with mg
  3gc2		1.85 angstrom crystal structure of o-succinylbenzoate synthase from salmonella typhimurium in complex with succinic acid
  3gd6		Crystal structure of divergent enolase from oceanobacillus iheyensis complexed with phosphate
  3go2		Crystal structure of putative l-alanine-dl-glutamate epimerase from burkholderia xenovorans strain lb400 bound to magnesium
  3gy1		Crystal structure of putative mandelate racemase/muconate lactonizing protein from clostridium beijerinckii ncimb
  3h12		Crystal structure of putative mandelate racemase from bordetella bronchiseptica rb50
  3h7v		Crystal structure of o-succinylbenzoate synthase from thermosynechococcus elongatus bp-1 complexed with mg in the active site
  3i4k		Crystal structure of muconate lactonizing enzyme from corynebacterium glutamicum
  3i6e		Crystal structure of muconate lactonizing enzyme from placeholder species
  3i6t		Crystal structure of muconate cycloisomerase from jannaschia sp.
  3ik4		Crystal structure of mandelate racemase/muconate lactonizing protein from herpetosiphon aurantiacus
  3muc		Muconate cycloisomerase variant i54v

• Links (links to other resources describing this domain)

• PFAM	MR_MLE
  INTERPRO	IPR013342

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