EzCatDB: D00267

DB codeD00267
RLCP classification5.104.2187000.9100
5.204.2187010.9090
CATH domainDomain 11.10.275.10Catalytic domain
Domain 21.20.200.10Catalytic domain
E.C.4.3.1.3
CSA1b8f

CATH domainRelated DB codes (homologues)
1.10.275.10T00086,T00092,T00094,T00095
1.20.200.10T00086,T00092,T00094,T00095

Enzyme Name
Swiss-protKEGG

P21310
Protein nameHistidine ammonia-lyasehistidine ammonia-lyase
histidase
histidinase
histidine alpha-deaminase
L-histidine ammonia-lyase
SynonymsHistidase
EC 4.3.1.3

KEGG pathways
MAP codePathways
MAP00340Histidine metabolism
MAP00910Nitrogen metabolism

Swiss-prot:Accession NumberP21310
Entry nameHUTH_PSEPU
ActivityL-histidine = urocanate + NH(3).
SubunitHomotetramer.
Subcellular locationCytoplasm (Potential).
Cofactor


SubstratesProductsintermediates
KEGG-idC00135C05167C00785C11823C00014
CompoundL-Histidinealpha-Amino acidUrocanate2,3-Ene acidNH3
Typeamino acids,aromatic ring (with nitrogen atoms)amino acidsaromatic ring (with nitrogen atoms),carboxyl groupcarboxyl groupamine group,organic ion
1b8fA01UnboundUnboundUnboundUnboundUnboundUnbound
1eb4A01UnboundUnboundUnboundUnboundUnboundUnbound
1gk2A01UnboundUnboundUnboundUnboundUnboundUnbound
1gk2B01UnboundUnboundUnboundUnboundUnboundUnbound
1gk2C01UnboundUnboundUnboundUnboundUnboundUnbound
1gk2D01UnboundUnboundUnboundUnboundUnboundUnbound
1gk3A01UnboundUnboundUnboundUnboundUnboundUnbound
1gkjA01UnboundUnboundUnboundUnboundUnboundUnbound
1gkmA01UnboundUnboundUnboundUnboundUnboundIntermediate-analogue:CYS-__O-SO4
1b8fA02UnboundUnboundUnboundUnboundUnboundUnbound
1eb4A02UnboundUnboundUnboundUnboundUnboundUnbound
1gk2A02UnboundUnboundUnboundUnboundUnboundUnbound
1gk2B02UnboundUnboundUnboundUnboundUnboundUnbound
1gk2C02UnboundUnboundUnboundUnboundUnboundUnbound
1gk2D02UnboundUnboundUnboundUnboundUnboundUnbound
1gk3A02UnboundUnboundUnboundUnboundUnboundUnbound
1gkjA02UnboundUnboundUnboundUnboundUnboundUnbound
1gkmA02UnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P21310 & literature [16]
pdbCatalytic residuesModified residuesMain-chain involved in catalysiscomment
1b8fA01       
SER 143(dehydroalanine-like)
ALA 142;GLY 144;GLY 196
142A-143S-144G forming 4-methylidene-imidazole-5-one (MIO)
1eb4A01       
SER 143(dehydroalanine-like)
ALA 142;GLY 144;GLY 196
142A-143S-144G forming 4-methylidene-imidazole-5-one (MIO)
1gk2A01SER 143
                            
ALA 142;GLY 144;GLY 196

1gk2B01SER 143
                            
ALA 142;GLY 144;GLY 196

1gk2C01SER 143
                            
ALA 142;GLY 144;GLY 196

1gk2D01SER 143
                            
ALA 142;GLY 144;GLY 196

1gk3A01SER 143
                            
ALA 142;GLY 144;GLY 196

1gkjA01       
SER 143(dehydroalanine-like)
ALA 142;GLY 144;GLY 196
142A-143S-144G forming 4-methylidene-imidazole-5-one (MIO)
1gkmA01       
SER 143(dehydroalanine-like)
ALA 142;GLY 144;GLY 196
142A-143S-144G forming 4-methylidene-imidazole-5-one (MIO)
1b8fA02TYR 280;PHE 329;GLU 414



1eb4A02TYR 280;       ;GLU 414


mutant F329A
1gk2A02TYR 280;       ;GLU 414


mutant F329G
1gk2B02TYR 280;       ;GLU 414


mutant F329G
1gk2C02TYR 280;       ;GLU 414


mutant F329G
1gk2D02TYR 280;       ;GLU 414


mutant F329G
1gk3A02TYR 280;PHE 329;GLU 414



1gkjA02       ;PHE 329;GLU 414


mutant Y280F
1gkmA02TYR 280;PHE 329;GLU 414




References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[8]Fig.6, Fig.7, p.4433
[10]Fig.4, Fig.5, p.5359-53604
[12]Fig.16, p.190-1954
[13]p.516-518, p.520
[14]Fig.5
[15]Fig.3
[16]Fig.7, p.1794-17963
[18]Figure 1A, p.622

references
[1]
PubMed ID4847567
JournalBiochim Biophys Acta
Year1974
Volume350
Pages354-7
AuthorsSawada S, Tanaka A, Yuzoinouye, Hirasawa T, Soda K
TitleBiostereochemistry of histidine metabolism. II. The steric course of ammonia elimation from L-histidine.
[2]
PubMed ID193832
JournalJ Biol Chem
Year1977
Volume252
Pages3234-9
AuthorsLamartiniere CA, Feigelson M
TitleEffects of estrogen, glucocorticoid, glucagon, and adenosine 3':5'-monophosphate on catalytic activity, amount, and rate of de novo synthesis of hepatic histidase.
[3]
PubMed ID3919759
JournalBiochemistry
Year1985
Volume24
Pages301-8
AuthorsConsevage MW, Phillips AT
TitlePresence and quantity of dehydroalanine in histidine ammonia-lyase from Pseudomonas putida.
[4]
CommentsACTIVE SITE.
Medline ID94058243
PubMed ID8239649
JournalArch Biochem Biophys
Year1993
Volume307
Pages126-32
AuthorsHernandez D, Stroh JG, Phillips AT
TitleIdentification of Ser143 as the site of modification in the active site of histidine ammonia-lyase.
Related Swiss-protP21310
[5]
PubMed ID8251759
JournalProtein Expr Purif
Year1993
Volume4
Pages473-8
AuthorsHernandez D, Phillips AT
TitlePurification and characterization of Pseudomonas putida histidine ammonia-lyase expressed in Escherichia coli.
[6]
CommentsACTIVE SITE, AND MUTAGENESIS.
Medline ID94296420
PubMed ID8024588
JournalBiochem Biophys Res Commun
Year1994
Volume201
Pages1433-8
AuthorsHernandez D, Phillips AT
TitleSer-143 is an essential active site residue in histidine ammonia-lyase of Pseudomonas putida.
Related Swiss-protP21310
[7]
CommentsACTIVE SITE, AND MUTAGENESIS.
Medline ID94263952
PubMed ID8204579
JournalBiochemistry
Year1994
Volume33
Pages6462-7
AuthorsLanger M, Reck G, Reed J, Retey J
TitleIdentification of serine-143 as the most likely precursor of dehydroalanine in the active site of histidine ammonia-lyase. A study of the overexpressed enzyme by site-directed mutagenesis.
Related Swiss-protP21310
[8]
PubMed ID8947915
JournalNaturwissenschaften
Year1996
Volume83
Pages439-47
AuthorsRetey J
TitleEnzymatic catalysis by Friedel-Crafts-type reactions.
[9]
PubMed ID9761874
JournalActa Crystallogr D Biol Crystallogr
Year1998
Volume54
Pages681-3
AuthorsTeo B, Kidd RD, Mack J, Tiwari A, Hernandez D, Phillips AT, Farber GK
TitleCrystallization and preliminary X-ray studies of Pseudomonas putida histidine ammonium-lyase.
[10]
CommentsX-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), AND REVISIONS TO 151 AND 438.
Medline ID99238310
PubMed ID10220322
JournalBiochemistry
Year1999
Volume38
Pages5355-61
AuthorsSchwede TF, Retey J, Schulz GE
TitleCrystal structure of histidine ammonia-lyase revealing a novel polypeptide modification as the catalytic electrophile.
Related PDB1b8f
Related Swiss-protP21310
[11]
PubMed ID10195286
JournalProtein Eng
Year1999
Volume12
Pages151-3
AuthorsSchwede TF, Badeker M, Langer M, Retey J, Schulz GE
TitleHomogenization and crystallization of histidine ammonia-lyase by exchange of a surface cysteine residue.
[12]
PubMed ID11665488
JournalAdv Protein Chem
Year2001
Volume58
Pages175-214
AuthorsLanger B, Langer M, Retey J
TitleMethylidene-imidazolone (MIO) from histidine and phenylalanine ammonia-lyase.
[13]
PubMed ID11578924
JournalCurr Opin Chem Biol
Year2001
Volume5
Pages512-24
AuthorsPoppe L
TitleMethylidene-imidazolone: a novel electrophile for substrate activation.
[14]
PubMed ID11732994
JournalEur J Biochem
Year2001
Volume268
Pages6011-9
AuthorsRother D, Poppe L, Viergutz S, Langer B, Retey J
TitleCharacterization of the active site of histidine ammonia-lyase from Pseudomonas putida.
[15]
PubMed ID11457276
JournalJ Am Chem Soc
Year2001
Volume123
Pages4679-86
AuthorsDonnelly M, Fedeles F, Wirstam M, Siegbahn PE, Zimmer M
TitleComputational analysis of the autocatalytic posttranslational cyclization observed in histidine ammonia-lyase. A comparison with green fluorescent protein.
[16]
PubMed ID11895450
JournalEur J Biochem
Year2002
Volume269
Pages1790-7
AuthorsBaedeker M, Schulz GE
TitleStructures of two histidine ammonia-lyase modifications and implications for the catalytic mechanism.
Related PDB1gkj,1gkm
[17]
CommentsHomologous enzyme
PubMed ID12071972
JournalEur J Biochem
Year2002
Volume269
Pages3065-75
AuthorsRother D, Poppe L, Morlock G, Viergutz S, Retey J
TitleAn active site homology model of phenylalanine ammonia-lyase from Petroselinum crispum.
[18]
PubMed ID11796111
JournalStructure (Camb)
Year2002
Volume10
Pages61-7
AuthorsBaedeker M, Schulz GE
TitleAutocatalytic peptide cyclization during chain folding of histidine ammonia-lyase.
Related PDB1eb4,1gk2,1gk3

comments
According to the literature [10], a prosthetic group, 4-methylidene-imidazole-5-one (MIO), which is formed from Ala-Ser-Gly at positions 142-144, makes an electrophile, which will be a target for a nucleophilic attack. The MIO group can be formed by two water elimination steps. At the first step, the nitrogen atom of Gly144 makes an intramolecular nucleophilic attack at the carbonyl group of Ala142, resulting in a cyclization. At the second step, a water is eliminated from the sidechain of Ser143, forming the MIO group.
According to the literature [10], [12], [13] & [16], the reaction proceeds as follows:
(A) Addition of imidazole ring to double-bond of MIO group:
(A1) The CD atom of the substrate imidazole ring makes a nucleophilic attack on the electrophilic methylidene group of the prosthetic MIO group, forming a covalent (single-bonded) intermediate between the substrate histidine and the MIO group.
(A2) The MIO group becomes aromatic with the 143-O anion stabilized by the amide of Gly196, whilst the positive charged imidazole is stabilized by the pi-electrons of Phe329.
(B) Isomerization (change in the position of double-bond):
(B1) Tyr280' from the adjacent chain acts as a general base, by abstracting H(re) proton from the beta-carbon, which is acidified by the positive charge of the imidazole ring. The oxygen atom of Tyr280' is hydrogen-bonded to Glu414, which seems to modulate the catalytic function of Tyr280'.
(C) Elimination of amine group from alpha-carbon is accompanied by elimination of imidazole ring from MIO group:
(C1) The rearrangement of the MIO group eliminates the ammonia from the alpha-carbon, generating a double-bond between the beta-carbon and the alpha-carbon. The eliminated ammonia is stabilzed by Tyr53/Asn195/Asn313, whilst 143-O anion is stabilized by the amide of Gly196 (see [16]).

createdupdated
2004-06-092009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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