DB code: S00155

RLCP classification 8.131.160500.80 : Isomerization
8.113.365000.100 : Isomerization
8.113.365001.100 : Isomerization
CATH domain 2.60.120.10 : Jelly Rolls Catalytic domain
E.C. 5.1.3.13
CSA 1dzr
M-CSA 1dzr
MACiE

CATH domain Related DB codes (homologues)
2.60.120.10 : Jelly Rolls S00145 D00842 D00843 T00255 M00216 T00101

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
O27818 dTDP-4-dehydrorhamnose 3,5-epimerase
EC 5.1.3.13
Thymidine diphospho-4-keto-rhamnose 3,5-epimerase
dTDP-4-keto-6-deoxyglucose 3,5-epimerase
dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase
dTDP-L-rhamnose synthase
NP_276896.1 (Protein)
NC_000916.1 (DNA/RNA sequence)
PF00908 (dTDP_sugar_isom)
[Graphical View]
P26394 dTDP-4-dehydrorhamnose 3,5-epimerase
EC 5.1.3.13
Thymidine diphospho-4-keto-rhamnose 3,5-epimerase
dTDP-4-keto-6-deoxyglucose 3,5-epimerase
dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase
dTDP-L-rhamnose synthase
NP_461039.1 (Protein)
NC_003197.1 (DNA/RNA sequence)
PF00908 (dTDP_sugar_isom)
[Graphical View]
O06330 dTDP-4-dehydrorhamnose 3,5-epimerase
EC 5.1.3.13
Thymidine diphospho-4-keto-rhamnose 3,5-epimerase
dTDP-4-keto-6-deoxyglucose 3,5-epimerase
dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase
dTDP-L-rhamnose synthase
NP_217982.1 (Protein)
NC_000962.3 (DNA/RNA sequence)
NP_338097.1 (Protein)
NC_002755.2 (DNA/RNA sequence)
YP_006516954.1 (Protein)
NC_018143.1 (DNA/RNA sequence)
PF00908 (dTDP_sugar_isom)
[Graphical View]
Q8GIQ0
DTDP-4-dehydrorhamnose 3,5-epimerase
EC 5.1.3.13
PF00908 (dTDP_sugar_isom)
[Graphical View]
Q9HU21 dTDP-4-dehydrorhamnose 3,5-epimerase
EC 5.1.3.13
Thymidine diphospho-4-keto-rhamnose 3,5-epimerase
dTDP-4-keto-6-deoxyglucose 3,5-epimerase
dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase
dTDP-L-rhamnose synthase
NP_253851.1 (Protein)
NC_002516.2 (DNA/RNA sequence)
PF00908 (dTDP_sugar_isom)
[Graphical View]

KEGG enzyme name
dTDP-4-dehydrorhamnose 3,5-epimerase
dTDP-L-rhamnose synthetase
dTDP-L-rhamnose synthetase
thymidine diphospho-4-ketorhamnose 3,5-epimerase
TDP-4-ketorhamnose 3,5-epimerase
dTDP-4-dehydro-6-deoxy-D-glucose 3,5-epimerase
TDP-4-keto-L-rhamnose-3,5-epimerase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
O27818 O27818_METTH
P26394 RFBC_SALTY dTDP-4-dehydro-6-deoxy-D-glucose = dTDP-4- dehydro-6-deoxy-L-mannose. Homodimer.
O06330 O06330_MYCTU
Q8GIQ0 Q8GIQ0_STRSU
Q9HU21 Q9HU21_PSEAE

KEGG Pathways
Map code Pathways E.C.
MAP00520 Nucleotide sugars metabolism
MAP00521 Streptomycin biosynthesis
MAP00523 Polyketide sugar unit biosynthesis

Compound table
Substrates Products Intermediates
KEGG-id C11907 C00688
E.C.
Compound 4,6-Dideoxy-4-oxo-dTDP-D-glucose dTDP-4-dehydro-6-deoxy-L-mannose
Type amide group,carbohydrate,nucleotide amide group,carbohydrate,nucleotide
ChEBI 16128
45868
PubChem 439292
443211
1ep0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1epzA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:TYD Unbound
1dzrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1dzrB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1dztA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:TPE Unbound
1dztB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:ATY Unbound
1pm7A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1pm7B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1upiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1nxmA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1nxmB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound
1nywA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:DAU Unbound
1nywB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:DAU Unbound
1nzcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:TDX Unbound
1nzcB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:TDX Unbound
1nzcC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:TDX Unbound
1nzcD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:TDX Unbound
1rtvA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:SRT Unbound

Reference for Active-site residues
resource references E.C.
literature [2], [3], [7], [8]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ep0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 51;HIS 64;LYS 73;TYR 133;ASP 172
1epzA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 51;HIS 64;LYS 73;TYR 133;ASP 172
1dzrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 50;HIS 63;LYS 73;TYR 133;ASP 170
1dzrB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 50;HIS 63;LYS 73;TYR 133;ASP 170
1dztA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 50;HIS 63;LYS 73;TYR 133;ASP 170
1dztB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 50;HIS 63;LYS 73;TYR 133;ASP 170
1pm7A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 49;HIS 62;LYS 72;TYR 132;ASP 171
1pm7B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 49;HIS 62;LYS 72;TYR 132;ASP 171
1upiA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 49;HIS 62;LYS 72;TYR 132;ASP 171 CME 134;CME 147(S,S-(2-hydroxyethyl)-thiocystein)
1nxmA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 63;HIS 76;LYS 82;TYR 140;ASP 180
1nxmB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 63;HIS 76;LYS 82;TYR 140;ASP 180
1nywA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 63;HIS 76;LYS 82;TYR 140;ASP 180
1nywB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 63;HIS 76;LYS 82;TYR 140;ASP 180
1nzcA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 63;HIS 76;LYS 82;TYR 140;ASP 180
1nzcB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 63;HIS 76;LYS 82;TYR 140;ASP 180
1nzcC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 63;HIS 76;LYS 82;TYR 140;ASP 180
1nzcD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 63;HIS 76;LYS 82;TYR 140;ASP 180
1rtvA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASN 49;HIS 62;LYS 71;TYR 131;ASP 168

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig.5, p.691-693 5
[3]
p.24612
[4]
p.401
[7]
Fig.4, p.718-721
[9]
p.32689

References
[1]
Resource
Comments
Medline ID
PubMed ID 9020123
Journal J Biol Chem
Year 1997
Volume 272
Pages 4121-8
Authors Koplin R, Brisson JR, Whitfield C
Title UDP-galactofuranose precursor required for formation of the lipopolysaccharide O antigen of Klebsiella pneumoniae serotype O1 is synthesized by the product of the rfbDKPO1 gene.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 11114506
Journal Curr Opin Struct Biol
Year 2000
Volume 10
Pages 687-96
Authors Giraud MF, Naismith JH
Title The rhamnose pathway.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10827167
Journal J Biol Chem
Year 2000
Volume 275
Pages 24608-12
Authors Christendat D, Saridakis V, Dharamsi A, Bochkarev A, Pai EF, Arrowsmith CH, Edwards AM
Title Crystal structure of dTDP-4-keto-6-deoxy-D-hexulose 3,5-epimerase from Methanobacterium thermoautotrophicum complexed with dTDP.
Related PDB 1ep0 1epz
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.17 ANGSTROMS).
Medline ID 20264521
PubMed ID 10802738
Journal Nat Struct Biol
Year 2000
Volume 7
Pages 398-402
Authors Giraud MF, Leonard GA, Field RA, Berlind C, Naismith JH
Title RmlC, the third enzyme of dTDP-L-rhamnose pathway, is a new class of epimerase.
Related PDB 1dzr 1dzt
Related UniProtKB P26394
[5]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12951098
Journal Bioorg Med Chem Lett
Year 2003
Volume 13
Pages 3227-30
Authors Babaoglu K, Page MA, Jones VC, McNeil MR, Dong C, Naismith JH, Lee RE
Title Novel inhibitors of an emerging target in Mycobacterium tuberculosis; substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis.
Related PDB 1pm7
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 12785757
Journal J Am Chem Soc
Year 2003
Volume 125
Pages 6348-9
Authors Leriche C, He X, Chang CW, Liu HW
Title Reversal of the apparent regiospecificity of NAD(P)H-dependent hydride transfer: the properties of the difluoromethylene group, a carbonyl mimic.
Related PDB
Related UniProtKB
[7]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 12791259
Journal Structure (Camb)
Year 2003
Volume 11
Pages 715-23
Authors Dong C, Major LL, Allen A, Blankenfeldt W, Maskell D, Naismith JH
Title High-resolution structures of RmlC from Streptococcus suis in complex with substrate analogs locate the active site of this class of enzyme.
Related PDB 1nxm 1nyw 1nzc
Related UniProtKB
[8]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 15103135
Journal Acta Crystallogr D Biol Crystallogr
Year 2004
Volume 60
Pages 895-902
Authors Kantardjieff KA, Kim CY, Naranjo C, Waldo GS, Lekin T, Segelke BW, Zemla A, Park MS, Terwilliger TC, Rupp B
Title Mycobacterium tuberculosis RmlC epimerase (Rv3465): a promising drug-target structure in the rhamnose pathway.
Related PDB 1upi
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 15159413
Journal J Biol Chem
Year 2004
Volume 279
Pages 32684-91
Authors Merkel AB, Major LL, Errey JC, Burkart MD, Field RA, Walsh CT, Naismith JH
Title The position of a key tyrosine in dTDP-4-Keto-6-deoxy-D-glucose-5-epimerase (EvaD) alters the substrate profile for this RmlC-like enzyme.
Related PDB
Related UniProtKB

Comments

According to the literature [2] & [7], this enzyme catalyzes two epimerization reactions, which are composed of four isomerization (shift of double-bond position) as follows:
Here, Asp170 (of 1dzr;PDB) modulates the activity of His63, whereas Asn50 modulates the activity of Tyr133.
(A) Shift of double-bond position from C4=O4 to C4=C5 (Isomerization):
(A1) His63 acts as a general base to deprotonate C5 atom, forming an enolate intermediate.
(A2) Lys73 stabilizes the negative charge on the O4 enolate intermediate.
(B) Shift of double-bond position from C4=C5 to C4=O4 (Isomerization):
(B1) Tyr133 acts as a general acid to protonate C5 atom from the opposite direction.
(B2) Here, there must be proton shuttle for His63 and Tyr133, since they will have to act as a general base and a general acid, respectively, in the next reaction. For Tyr133, a water bound to the residue might provide a new proton. Also for His63, a water molecule, which is hydrogen bonded to this residue, forms a wide network, suggesting a proton shuttle for it.
(C) Shift of double-bond position from C4=O4 to C4=C3 (Isomerization):
(C1) His63 acts as a general base to deprotonate C3 atom, forming an enolate intermediate.
(C2) Lys73 stabilizes the negative charge on the O4 enolate intermediate.
(D) Shift of double-bond position from C4=C3 to C4=O4 (Isomerization):
(D1) Tyr133 acts as a general acid to protonate C5 atom through a water from the opposite direction.
(D2) Here, there must be proton shuttle for His63 and Tyr133, since they will have to act as a general base and a general acid, respectively, for a next substrate. For Tyr133, a water bound to the residue might provide a new proton. Also for His63, a water molecule, which is hydrogen bonded to this residue, forms a wide network, suggesting a proton shuttle for it.

Created Updated
2004-04-06 2009-03-17