Entry
Name
D-Ala-D-Ala dipeptidase;
D-alanyl-D-alanine dipeptidase;
vanX D-Ala-D-Ala dipeptidase;
VanX
Class
Hydrolases;
Acting on peptide bonds (peptidases);
Dipeptidases
BRITE hierarchy
Reaction(IUBMB)
D-Ala-D-Ala + H2O = 2 D-Ala [RN:
R07651 ]
Reaction(KEGG)
Substrate
Product
Comment
A Zn2+-dependent enzyme [4]. The enzyme protects Enterococcus faecium from the antibiotic vancomycin, which can bind to the -D-Ala-D-Ala sequence at the C-terminus of the peptidoglycan pentapeptide (see diagram). This enzyme reduces the availability of the free dipeptide D-Ala-D-Ala, which is the precursor for this pentapeptide sequence, allowing D-Ala-(R)-lactate (for which vancomycin has much less affinity) to be added to the cell wall instead [2,3]. The enzyme is stereospecific, as L-Ala-L-Ala, D-Ala-L-Ala and L-Ala-D-Ala are not substrates [2]. Belongs in peptidase family M15.
History
EC 3.4.13.22 created 2006
Orthology
K08641 zinc D-Ala-D-Ala dipeptidase
K18866 zinc D-Ala-D-Ala dipeptidase/carboxypeptidase
Genes
ECW : EcE24377A_1677(ddpX)
EDJ : ECDH1ME8569_1431(ddpX)
REE : electrica_01068(ddpX)
SFJ : SAMEA4384070_2424(ddpX)
SOF : NCTC11214_04342(ddpX)
TPTY : NCTC11468_00485(ddpX)
XPH : XppCFBP6546_15110(XppCFBP6546P_15110)
XHD : LMG31886_39940(vanX)
PMUI : G4G71_06700 G4G71_09530
PNT : G5B91_25300 G5B91_28720
PPRC : PFLCHA0_c40820(ddpX)
PDR : H681_18785 H681_21470
PKC : PKB_1066 PKB_5123(vanX)
PYM : AK972_2044 AK972_2211
PTRL : OU419_21960 OU419_24715
PDEN : F1C79_17010 F1C79_20215
TACT : SG35_010210 SG35_012410
ASIP : AQUSIP_09590(ddpX) AQUSIP_09710(vanX)
LPN : lpg2449 lpg2585(pcgL)
LPH : LPV_2773 LPV_2917(vanX)
LPO : LPO_2639 LPO_2852(vanX)
LPU : LPE509_00454 LPE509_00615
LPM : LP6_2478(ddpX) LP6_2616(pcgL)
LPA : lpa_03417 lpa_03568(ddpX) lpa_03780(ddpX)
LLO : LLO_1611 LLO_1639 LLO_2675 LLO_2917
LHA : LHA_0456 LHA_2877(vanX)
LLG : 44548918_00346(ddpX_1) 44548918_02386(ddpX_2)
LJR : NCTC11533_00360(vanX) NCTC11533_02556(ddpX)
LCJ : NCTC11976_00284(ddpX)
LWA : SAMEA4504053_0564(ddpX_1) SAMEA4504053_2427(ddpX_2)
LSS : NCTC12082_01727(ddpX_1) NCTC12082_01816(ddpX_2)
LADL : NCTC12735_01374(ddpX)
LANT : TUM19329_06510(pcgL)
LCAD : PXX05_00375 PXX05_11465
TMC : LMI_0349(vanX) LMI_1375
MISZ : MishRS11D_21770(ddpX)
ALV : Alvin_0996 Alvin_0999 Alvin_3183
HSI : BOX17_06935 BOX17_14560
HBH : E4T21_19175 E4T21_19360
ENW : MJO57_20065(ddpX) MJO57_20075(ddpX)
ENG : O2T12_16875(ddpX) O2T12_16890(ddpX)
OPE : PU634_04075 PU634_12150
ZDF : AN401_03945 AN401_06745
WCN : PE074_06150 PE074_09315(ddpX)
CVI : CV_0902(vanX) CV_3935
CHRI : DK842_04860 DK842_12100
CHRB : DK843_10385 DK843_17535
CRZ : D1345_04980 D1345_11845
CHAE : CH06BL_10760 CH06BL_24310
BMN : BMA10247_A1051(dppX)
BPM : BURPS1710b_A2563(vanX)
BPL : BURPS1106A_A1312(ddpX)
BPD : BURPS668_A1393(vanX)
BUR : Bcep18194_B0891 Bcep18194_B1254
BCM : Bcenmc03_5471 Bcenmc03_5715
BCH : Bcen2424_4590 Bcen2424_4812
BCEP : APZ15_28810 APZ15_30135
BCON : NL30_02225 NL30_03290
BSEM : WJ12_28830 WJ12_30145
BMEC : WJ16_27645 WJ16_28680
BSTG : WT74_18245 WT74_27915
BARI : NLX30_27305 NLX30_29275(ddpX)
BAEN : L3V59_22795(ddpX) L3V59_24475
BURK : DM992_21570 DM992_31705
BXB : DR64_7091(ddpX) DR64_8229(ddpX)
PCJ : CUJ87_27305 CUJ87_30830
PEW : KZJ38_12670(ddpX) KZJ38_33645
PDIO : PDMSB3_1278.1(ddpX)
PSAA : QEN71_15570(ddpX) QEN71_34870
PLG : NCTC10937_02132(ddpX)
URU : DSM104443_01529(ddpX)
UPL : DSM104440_01439(ddpX)
RTL : H6P87_00319(vanXB) H6P87_01163(ddpX)
REN : EF513_05820 EF513_07680
VGO : GJW-30_1_00787(vanX)
LNE : FZC33_24545 FZC33_25250
MTUN : MTUNDRAET4_2033(ddpX)
TSV : DSM104635_00989(ddpX) DSM104635_02016(vanX)
KHA : IFJ82_08715 IFJ82_10455(ddpX)
GSO : PH603_03455 PH603_12265
DALK : DSCA_53210 DSCA_53430
DTI : Desti_1921 Desti_5152
PIJ : QEJ31_07010 QEJ31_10725
BBE : BBR47_05880 BBR47_12370
BFM : BP422_01430 BP422_28595
BAYD : BSPP4475_08380(vanX)
BBOR : RFB14_19940 RFB14_20025
BRUM : NDK47_11550 NDK47_20705 NDK47_20790
PBJ : VN24_01310 VN24_07225
PALR : HGI30_04875 HGI30_12760
PMAE : LMZ02_20970(vanX) LMZ02_28660
PSPN : L1F29_01960 L1F29_14075
LNN : F0161_00725 F0161_09345
LPD : AYR62_10705 AYR62_15350
LMAE : FGL90_04230 FGL90_05415
EFC : EFAU004_02774(vanXB)
EFAU : EFAU085_00736(vanXB)
ESG : EsVE80_p1-00090(vanX)
CLB : Clo1100_0663 Clo1100_2029
PFAA : MM59RIKEN_06550 MM59RIKEN_12800(vanY) MM59RIKEN_24460
VCOP : MM50RIKEN_08110(vanY)
FWA : DCMF_01545 DCMF_02705
IBU : IB211_00655 IB211_01761
EUU : ADJ67_01660 ADJ67_03765
ACEL : acsn021_25820(vanY)
ACHT : bsdcttw_22900(vanY_1) bsdcttw_27600(vanY_2)
AMIC : Ami3637_03095 Ami3637_13570(vanX)
ABUT : Ami103574_02980 Ami103574_06130 Ami103574_07965
ETM : CE91St48_02950(vanY) CE91St48_40230(ddpX)
PDC : CDIF630_01804(vanY1)
PDF : CD630DERM_16270(vanY)
SRI : SELR_pSRC101300(vanX)
PFAC : PFJ30894_02013(ddpX)
LCG : L3BBH23_19230(vanXB)
MMAE : MMARE11_46300(lpqR)
MHAD : B586_05625 B586_10005
MPAG : C0J29_02835 C0J29_03365 C0J29_26410
MBAI : MB901379_04211(ddpX)
MHEK : JMUB5695_00932(lpqR)
MSPG : F6B93_01905 F6B93_19210
MPHL : MPHLCCUG_00631(ddpX)
MVQ : MYVA_1601 MYVA_5064(lpqR)
MLL : B1R94_13245 B1R94_19660
MAUU : NCTC10437_04942(ddpX)
MARZ : MARA_28690 MARA_52960
MANY : MANY_02580 MANY_14070
MPOF : MPOR_48040 MPOR_52810
MSEI : MSEDJ_23120 MSEDJ_57000
MFLV : NCTC10271_00574(ddpX)
MSAL : DSM43276_01605(ddpX)
MTER : 4434518_01943(ddpX)
NWL : NWFMUON74_45710(vanA)
SCO : SCO1396(SC1A8A.16c) SCO2328(SCC53.19) SCO3596(SC66T3.07)
SCYE : R2B67_17745 R2B67_31705
SVL : Strvi_1426 Strvi_5702 Strvi_9340
SRC : M271_18335 M271_25650 M271_43685
SMAL : SMALA_0671 SMALA_5061
STRP : F750_1141 F750_6452
SLV : SLIV_20315(vanX) SLIV_26040 SLIV_30780
SVT : SVTN_03045 SVTN_06350
STRE : GZL_02161 GZL_07463
SLD : T261_07487 T261_5666
SLC : SL103_06905 SL103_13690
SXI : SXIM_06730 SXIM_54610
STRM : M444_07150 M444_35025
STRC : AA958_01615 AA958_28370
SAMB : SAM23877_0338 SAM23877_1454
SCX : AS200_06585 AS200_36705 AS200_44880
SRW : TUE45_pSRc_0325(ddpX)
SLE : sle_01160(sle_01160) sle_57010(sle_57010)
SPAV : Spa2297_03320 Spa2297_05150
SALW : CP975_02235 CP975_05035
SCAD : DN051_07295 DN051_31785
SLS : SLINC_1579 SLINC_1843 SLINC_7674
SNR : SNOUR_09685 SNOUR_34330
SALU : DC74_1682 DC74_6104
SALL : SAZ_08945 SAZ_31455
SNW : BBN63_29755 BBN63_34025
SGV : B1H19_07740 B1H19_14140
SALF : SMD44_00245(vanX) SMD44_01409(vanX)
SALJ : SMD11_5696(vanX) SMD11_6976
SLX : SLAV_03520 SLAV_30760(vanX)
SFK : KY5_0472c KY5_1125 KY5_7836
SGD : ELQ87_04485 ELQ87_32845
SKA : CP970_00250 CP970_37195 CP970_40415
SHAW : CEB94_07250 CEB94_33725
SAQU : EJC51_03790(vanX) EJC51_09505 EJC51_16710
SSEO : D0Z67_02465 D0Z67_03070
SBY : H7H31_02100 H7H31_16170(vanX) H7H31_16470
SRIM : CP984_35635 CP984_39915(vanX)
SPHV : F9278_13670 F9278_43130
SCHA : CP983_36275 CP983_39425
SGX : H4W23_03855 H4W23_06865
SBAT : G4Z16_14910 G4Z16_30590
SSPB : CP982_05345 CP982_08220 CP982_31315(vanX) CP982_40590
SPLA : CP981_04965 CP981_12390
SPRA : CP972_06080 CP972_31600
SROI : IAG44_02355 IAG44_33580 IAG44_39580(vanX)
SXN : IAG42_01120 IAG42_30120
SHK : J2N69_02430 J2N69_04970
SANU : K7396_24870 K7396_31120
SINE : KI385_07375 KI385_15215
SDEC : L3078_03285 L3078_15130
SAOV : G3H79_31865 G3H79_33180
SDUR : M4V62_35185 M4V62_38720 M4V62_40790
SYAN : NRK68_05895 NRK68_29235
SRUG : F0345_03070 F0345_27990
SAKB : K1J60_29675 K1J60_43385
STAA : LDH80_05495 LDH80_32625
SCAE : IHE65_30425 IHE65_43365
SSPN : LXH13_06875 LXH13_34740(vanX)
SXT : KPP03845_101593(vanXB)
STUD : STRTU_004931 STRTU_006304
SANT : QR300_08115 QR300_37260
SYUN : MOV08_09605 MOV08_34575
SCOA : QU709_01075 QU709_36775 QU709_45510(vanX)
SFP : QUY26_34235 QUY26_38945
SINN : ABB07_31860 ABB07_36225
STRZ : OYE22_02130 OYE22_15915(vanX) OYE22_16220
PSIC : J4E96_04775 J4E96_04945 J4E96_14340
NOO : FE634_07190 FE634_17695
NAQU : ENKNEFLB_02182(vanXB)
KQI : F1D05_24240 F1D05_26440(vanX)
SPIQ : OHA34_10795 OHA34_26515(vanX)
ACTQ : OG417_35815 OG417_48870
NOA : BKM31_13725 BKM31_33780
NCX : Nocox_10295(ddpX1) Nocox_20140(ddpX2)
NGN : LCN96_11630 LCN96_29460
NFS : OIE67_03585 OIE67_35385
AMD : AMED_0659(vanA) AMED_8288(vanA)
AMM : AMES_0657(vanA) AMES_8160(vanA)
AMZ : B737_0658(vanA) B737_8161(vanA)
AOI : AORI_1473(vanX) AORI_2227(vanX)
AJA : AJAP_27755 AJAP_32165(vanX)
AMYC : CU254_05725 CU254_15950
AMYB : BKN51_37400 BKN51_41400
AAB : A4R43_21430 A4R43_33690
AMYY : YIM_33815(ddpX) YIM_36540(vanX1) YIM_44415(vanX2)
AORI : SD37_33755 SD37_37960
APRT : MUY14_04910(vanX) MUY14_33495
KBU : Q4V64_03530 Q4V64_08610 Q4V64_46360(vanX)
KPHY : AOZ06_08685 AOZ06_28870
CROS : N8J89_03405(vanX) N8J89_22080
MICB : MicB006_1026 MicB006_2451
MTUA : CSH63_08095 CSH63_19590
MTEM : GCE86_12920 GCE86_30420
VMA : VAB18032_09600 VAB18032_19945
VER : HUT12_05755 HUT12_17545
MENO : Jiend_18790 Jiend_59080(vanA)
MCHL : PVK74_07200 PVK74_26170
MPRN : Q3V37_02150 Q3V37_20015
MHAW : RMN56_06725 RMN56_24965
PFLA : Pflav_001160 Pflav_014270 Pflav_032710
PSUU : Psuf_054830(vanA) Psuf_064030 Psuf_064040
DHI : LH044_08550(vanX) LH044_18165
SYY : SYNGTS_1787(slr1679)
SYT : SYNGTI_1787(slr1679)
SYS : SYNPCCN_1786(slr1679)
SYQ : SYNPCCP_1786(slr1679)
SYR : SynRCC307_1270(ddpX)
SYX : SynWH7803_1320(ddpX)
SYNW : SynWH8103_01237(ddpX)
CEP : Cri9333_2538 Cri9333_4462
LEN : LEP3755_00070 LEP3755_56150
LET : O77CONTIG1_04608(ddpX)
LBO : LBWT_44490 LBWT_51470
KOV : K9N68_07130 K9N68_08080
SYP : SYNPCC7002_A2266(ddpX)
SYNN : NIES970_21270(ddpX)
ARP : NIES39_A06450 NIES39_D02990
PAGH : NIES204_30840 NIES204_43110
PPSU : NO713_00726(ddpX) NO713_00796(ddpX)
PRUN : PCC7821_03165(ddpX) PCC7821_04405(ddpX)
MVAG : D0A34_15285 D0A34_21720
LFS : HFV01_20395 HFV01_30460
OAC : Oscil6304_0331 Oscil6304_0629
ONI : Osc7112_0237 Osc7112_1789
MIC : Mic7113_1328 Mic7113_2213
GLJ : GKIL_1509(vanX) GKIL_1879(vanX)
GML : ISF26_00140 ISF26_08475
NOE : CLI64_06505 CLI64_16205
CSG : Cylst_0054 Cylst_5626
NSPH : BDGGKGIB_03377(ddpX)
TOQ : HCG51_07900 HCG51_23885
FGI : OP10G_0233 OP10G_0542 OP10G_3162
NPY : NPRO_15330 NPRO_24970
ABIW : Abiwalacus_01140(vanA)
ROO : G5S37_14800 G5S37_19455
LCRE : Pla8534_39890(ddpX)
PPIO : CE91St28_21600(vanA)
BTHO : Btheta7330_00113(ddpX)
BCEL : BcellWH2_03030(ddpX)
PCRE : NCTC12858_01521(ddpX)
PCAG : NCTC12856_00777(ddpX)
PMZ : HMPREF0659_A5051(ddpX)
PDN : HMPREF9137_0631(ddpX)
POC : NCTC13071_00388(ddpX)
HHY : Halhy_1691 Halhy_3604
SMIZ : 4412673_03003(vanX)
SDJ : NCTC13534_04257(vanX)
STHA : NCTC11429_03438(vanX)
SPIR : CWM47_04995 CWM47_18980
SPIK : EXU85_07170 EXU85_29195
SFOL : H3H32_21215 H3H32_24435
PSEZ : HME7025_00025(vanX)
RSI : Runsl_2040 Runsl_2386
FMM : LVD15_07710 LVD15_23575
CHG : AXF12_03095 AXF12_10870
PHG : KCTC32516_01514(vanXB)
AALG : AREALGSMS7_00187(ddpX)
KOS : KORDIASMS9_02421(vanX)
KAN : IMCC3317_41860(vanXB)
SPON : HME9304_00728(vanX) HME9304_02789
» show all
Taxonomy
Reference
Authors
Reynolds PE, Depardieu F, Dutka-Malen S, Arthur M, Courvalin P
Title
Glycopeptide resistance mediated by enterococcal transposon Tn1546 requires production of VanX for hydrolysis of D-alanyl-D-alanine.
Journal
Sequence
Reference
Authors
Wu Z, Wright GD, Walsh CT
Title
Overexpression, purification, and characterization of VanX, a D-, D-dipeptidase which is essential for vancomycin resistance in Enterococcus faecium BM4147.
Journal
Sequence
Reference
Authors
McCafferty DG, Lessard IA, Walsh CT.
Title
Mutational analysis of potential zinc-binding residues in the active site of the enterococcal D-Ala-D-Ala dipeptidase VanX.
Journal
Reference
Authors
Bussiere DE, Pratt SD, Katz L, Severin JM, Holzman T, Park CH.
Title
The structure of VanX reveals a novel amino-dipeptidase involved in mediating transposon-based vancomycin resistance.
Journal
Reference
Authors
Tan AL, Loke P, Sim TS
Title
Molecular cloning and functional characterisation of VanX, a D-alanyl-D-alanine dipeptidase from Streptomyces coelicolor A3(2).
Journal
Sequence
Reference
Authors
Matthews ML, Periyannan G, Hajdin C, Sidgel TK, Bennett B, Crowder MW.
Title
Probing the reaction mechanism of the D-ala-D-ala dipeptidase, VanX, by using stopped-flow kinetic and rapid-freeze quench EPR studies on the Co(II)-substituted enzyme.
Journal
Other DBs
ExPASy - ENZYME nomenclature database: 3.4.13.22