Valacyclovir-hydrolase
Relationship
Comment
Biphenyl hydrolase-like; BPHL, Valacyclovirase, Mucin-associated antigen, MCNAA, Breast epithelial Mucin-associated antigen. Alpha-amino acid ester hydrolase that prefers small, hydrophobic, and aromatic side chains and does not have a stringent requirement for the leaving group other than preferring a primary alcohol. Valacyclovir (VACV) is the 5-prime valyl ester prodrug of acyclovir, an effective antiherpetic drug. VACV is relatively stable in gut lumen while very susceptible to intracellular enzymatic hydrolysis.
Database
Interpro : No interpro
PIRSF : No PIRSF
Pdoc : No Pdoc
Pfam : PF12697 Abhydrolase_6
Prints : No Print
EC Number : No EC Number
Sequences
| Peptide in | Fasta |
| Nucleotide in | Fasta |
| Alignment with Multalin | Text only |
| Seed alignment with MAFFT | No colour / coloured with Mview |
| Alignment with MAFFT | No colour / coloured with Mview |
| Dendrogram | The dnd file |
| Structure | Name | Proteins |
|---|---|---|
| 2OCG | Crystal structure of valacyclovir hydrolase | human-BPHL |
| 2OCI | Crystal structure of valacyclovir hydrolase complexed with a product analogue | human-BPHL |
| 2OCK | Crystal structure of valacyclovir hydrolase D123N mutant | human-BPHL |
| 2OCL | Crystal structure of valacyclovir hydrolase S122A mutant | human-BPHL |
| Gene_locus | Name | Species |
|---|---|---|
| 9acar-g3msq0 | Amblyomma maculatum (Gulf Coast tick) Putative uncharacterized protein | Amblyomma maculatum |
| 9chlr-e1iig9 | Oscillochloris trichoides DG-6 Alpha\/beta hydrolase fold protein | Oscillochloris trichoides DG-6 |
| acrec-f4wfr0 | Acromyrmex echinatior (Panamanian leafcutter ant) (Acromyrmex octospinosus echinatior) Valacyclovir hydrolase | Acromyrmex echinatior |
| acypi-c4wtq7 | Acyrthosiphon pisum (Pea aphid) ACYPI007493 protein | Acyrthosiphon pisum |
| acypi-c4wvd9 | Acyrthosiphon pisum (Pea aphid) ACYPI003684 protein | Acyrthosiphon pisum |
| aedae-q16si8 | Aedes aegypti (Yellowfever mosquito) (Culex aegypti) Esterase, putative | Aedes aegypti |
| ailme-g1m769 | Ailuropoda melanoleuca (Giant panda) Uncharacterized protein | Ailuropoda melanoleuca |
| ampqe-i1fjj6 | Amphimedon queenslandica (Sponge) Uncharacterized protein | Amphimedon queenslandica |
| ampqe-i1flz5 | Amphimedon queenslandica (Sponge) Uncharacterized protein | Amphimedon queenslandica |
| ampqe-i1g7p6 | Amphimedon queenslandica (Sponge) Uncharacterized protein | Amphimedon queenslandica |
| ampqe-i1g7p7 | Amphimedon queenslandica (Sponge) Uncharacterized protein | Amphimedon queenslandica |
| ampqe-i1gbn7 | Amphimedon queenslandica (Sponge) Uncharacterized protein | Amphimedon queenslandica |
| anoca-h9gpi8 | Anolis carolinensis (Green anole) (American chameleon) Uncharacterized protein | Anolis carolinensis |
| anoga-AGCG47202 | Anopheles gambiae str. PEST agcp10097 (fragment) | Anopheles gambiae |
| apime-h9k1r0 | Apis mellifera (Honeybee) Uncharacterized protein | Apis mellifera |
| ascsu-f1l5n5 | Ascaris suum (Pig roundworm) (Ascaris lumbricoides) Valacyclovir hydrolase | Ascaris suum |
| bommo-g8fpz6 | Bombyx mori (Silk moth) Bphl-like protein | Bombyx mori |
| bovin-q2kix6 | Bos taurus (Bovine) Biphenyl hydrolase-like Serine hydrolase\; breast epithelial mucin-associated antigen | Bos taurus |
| brafl-c3ygg6 | Branchiostoma floridae (Florida lancelet) (Amphioxus) Putative uncharacterized protein | Branchiostoma floridae |
| bruma-a8q632 | Brugia malayi (Filarial nematode worm) Alpha\/beta hydrolase, putative | Brugia malayi |
| caebe-g0n4q8 | Caenorhabditis brenneri (Nematode worm) Putative uncharacterized protein | Caenorhabditis brenneri |
| caebr-a8x3t6 | Caenorhabditis briggsae Protein CBG07052 | Caenorhabditis briggsae |
| caeel-K01A2.5 | Caenorhabditis elegans k01a2.5 protein | Caenorhabditis elegans |
| caere-e3mdg1 | Caenorhabditis remanei (Caenorhabditis vulgaris) Putative uncharacterized protein | Caenorhabditis remanei |
| calja-f7ecx5 | Callithrix jacchus (White-tufted-ear marmoset) Uncharacterized protein | Callithrix jacchus |
| camfo-e2aqx6 | Camponotus floridanus (Florida carpenter ant) Valacyclovir hydrolase | Camponotus floridanus |
| canfa-e2rgi0 | Canis lupus familiaris (Dog) (Canis familiaris) Uncharacterized protein | Canis lupus familiaris |
| cavpo-h0uyf1 | Cavia porcellus (Guinea pig) Uncharacterized protein | Cavia porcellus |
| chick-f1p4c6 | Gallus gallus (Chicken) Uncharacterized protein | Gallus gallus |
| chlad-b8gcj4 | Chloroflexus aggregans (strain MD-66 \/ DSM 9485) Alpha\/beta hydrolase fold protein | Chloroflexus aggregans |
| cioin-f6u176 | Ciona intestinalis (Transparent sea squirt) (Ascidia intestinalis) Uncharacterized protein | Ciona intestinalis |
| cioin-f6vac9 | Ciona intestinalis (Transparent sea squirt) (Ascidia intestinalis) Uncharacterized protein | Ciona intestinalis |
| cioin-f6xa69 | Ciona intestinalis (Transparent sea squirt) (Ascidia intestinalis) Uncharacterized protein | Ciona intestinalis |
| ciosa-h2yma2 | Ciona savignyi (Pacific transparent sea squirt) Uncharacterized protein | Ciona savignyi |
| closi-g7yk59 | Clonorchis sinensis (Chinese liver fluke) Valacyclovir hydrolase | Clonorchis sinensis |
| crigr-g3ieg5 | Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus) Valacyclovir hydrolase | Cricetulus griseus |
| culqu-b0w3i6 | Culex quinquefasciatus (Southern house mosquito) (Culex pungens) Bphl protein | Culex quinquefasciatus |
| danre-Q7ZVE1 | Danio rerio (Zebrafish) (Brachydanio rerio) similar to biphenyl hydrolase-like | Danio rerio |
| danre-h9gyq0 | Danio rerio (Zebrafish) (Brachydanio rerio) Biphenyl hydrolase like | Danio rerio |
| droan-b3mtj5 | Drosophila ananassae (Fruit fly) GF22862 | Drosophila ananassae |
| droer-b3p7h9 | Drosophila erecta (Fruit fly) GG12512 | Drosophila erecta |
| drogr-b4jsb2 | Drosophila grimshawi (Fruit fly) (Idiomyia grimshawi) GH18465 | Drosophila grimshawi |
| drome-CG5377 | Drosophila melanogaster (Fruit fly) cg5377 protein | Drosophila melanogaster |
| dromo-b4kc20 | Drosophila mojavensis (Fruit fly) GI10790 | Drosophila mojavensis |
| drope-b4g4p7 | Drosophila persimilis (Fruit fly) GL23336 | Drosophila persimilis |
| drops-q298u8 | Drosophila pseudoobscura (Fruit fly) ga18833-pa (fragment) | Drosophila pseudoobscura |
| drose-b4he97 | Drosophila sechellia (Fruit fly) GM23646 | Drosophila sechellia |
| drosi-b4r025 | Drosophila simulans (Fruit fly) GD18455 | Drosophila simulans |
| drovi-b4mb87 | Drosophila virilis (Fruit fly) GJ14388 | Drosophila virilis |
| drowi-b4nae3 | Drosophila willistoni (Fruit fly) GK11394 | Drosophila willistoni |
| droya-b4pma3 | Drosophila yakuba (Fruit fly) GE24034 | Drosophila yakuba |
| gasac-g3nmi2 | Gasterosteus aculeatus (Three-spined stickleback) Uncharacterized protein | Gasterosteus aculeatus |
| glomm-d3tlg8 | Glossina morsitans morsitans (Savannah tsetse fly) Putative hydrolase | Glossina morsitans morsitans |
| gorgo-g3ra28 | Gorilla gorilla gorilla (Lowland gorilla) Uncharacterized protein | Gorilla gorilla gorilla |
| harsa-e2btb0 | Harpegnathos saltator (Jerdon's jumping ant) Valacyclovir hydrolase | Harpegnathos saltator |
| hetgl-Q9BJ53 | Heterodera glycines putative alpha\/beta hydrolase | Heterodera glycines |
| horse-f6r958 | Equus caballus (Horse) Uncharacterized protein | Equus caballus |
| human-BPHL |  Homo sapiens (Human) biphenyl hydrolase-like DJ40E16.6.3, breast epithelial mucin-associated antigen AG BPHL (mcnaa), Valacyclovir hydrolase VACVase |
Homo sapiens |
| latch-h3aqv8 | Latimeria chalumnae (West Indian ocean coelacanth) Uncharacterized protein | Latimeria chalumnae |
| lepsm-c1bs44 | Lepeophtheirus salmonis (salmon louse) Valacyclovir hydrolase | Lepeophtheirus salmonis |
| loxaf-g3t4x8 | Loxodonta africana (African elephant) Uncharacterized protein | Loxodonta africana |
| macfa-g7p4b9 | Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey) Valacyclovir hydrolase | Macaca fascicularis |
| macmu-f6the6 | Macaca mulatta (Rhesus macaque) Valacyclovir hydrolase | Macaca mulatta |
| melga-g1myh1 | Meleagris gallopavo (Common turkey) Uncharacterized protein | Meleagris gallopavo |
| mondo-f7fg16 | Monodelphis domestica (Gray short-tailed opossum) Uncharacterized protein | Monodelphis domestica |
| mouse-bphl | Mus musculus (Mouse) biphenyl hydrolase-like, breast epithelial mucin-assoc AG BPHL (mcnaa), Valacyclovir hydrolase 2010012d11 rik protein | Mus musculus |
| myolu-g1ptz8 | Myotis lucifugus (Little brown bat) Uncharacterized protein | Myotis lucifugus |
| nemve-a7rfc6 | Nematostella vectensis (Starlet sea anemone) Predicted protein | Nematostella vectensis |
| nomle-g1rjt9 | Nomascus leucogenys (Northern white-cheeked gibbon) (Hylobates leucogenys) Uncharacterized protein | Nomascus leucogenys |
| oikdi-e4xgg8 | Oikopleura dioica (Tunicate) Whole genome shotgun assembly, reference scaffold set, scaffold scaffold_34 | Oikopleura dioica |
| oreni-i3jgr9 | Oreochromis niloticus (Nile tilapia) (Tilapia nilotica) Uncharacterized protein | Oreochromis niloticus |
| oryla-h2mbn6 | Oryzias latipes (Medaka fish) (Japanese ricefish) Uncharacterized protein | Oryzias latipes |
| osmmo-c1bin2 | Osmerus mordax (Rainbow smelt) (Atherina mordax) Valacyclovir hydrolase | Osmerus mordax |
| otoga-h0wwe7 | Otolemur garnettii (Small-eared galago) (Garnett's greater bushbaby) Uncharacterized protein | Otolemur garnettii |
| pantr-h2qs80 | Pan troglodytes (Chimpanzee) Uncharacterized protein | Pan troglodytes |
| phyit-d0p0z1 | Phytophthora infestans (strain T30-4) (Potato late blight fungus) Putative uncharacterized protein | Phytophthora infestans |
| phyrm-h3hcf9 | Phytophthora ramorum (Sudden oak death agent) Uncharacterized protein | Phytophthora ramorum |
| physp-g4zwy9 | Phytophthora sojae (strain P6497) (Soybean stem and root rot agent) (Phytophthora megasperma f. sp. glycines) Putative uncharacterized protein | Phytophthora sojae |
| pig-f1rwy7 | Sus scrofa (Pig) Uncharacterized protein | Sus scrofa |
| ponab-h2phs2 | Pongo abelii (Sumatran orangutan) Uncharacterized protein | Pongo abelii |
| pripa-h3f8r5 | Pristionchus pacificus Uncharacterized protein | Pristionchus pacificus |
| rabit-g1sxz9 | Oryctolagus cuniculus (Rabbit) Uncharacterized protein | Oryctolagus cuniculus |
| ratno-q3b8n9 | Rattus norvegicus (Rat) biphenyl hydrolase-like , breast epithelial mucin-assoc AG BPHL | Rattus norvegicus |
| solin-e9iyr6 | Solenopsis invicta (Red imported fire ant) (Solenopsis wagneri) Putative uncharacterized protein | Solenopsis invicta |
| spetr-i3lyt0 | Spermophilus tridecemlineatus (Thirteen-lined ground squirrel) (Ictidomys tridecemlineatus) Uncharacterized protein | Spermophilus tridecemlineatus |
| stanl-d3puq6 | Stackebrandtia nassauensis (strain DSM 44728 \/ NRRL B-16338 \/ NBR 102104 \/ LLR-40K-21) Alpha\/beta hydrolase fold protein | Stackebrandtia nassauensis |
| strpu-h3iwu2 | Strongylocentrotus purpuratus (Purple sea urchin) Uncharacterized protein | Strongylocentrotus purpuratus |
| taegu-b5fyu7 | Taeniopygia guttata (Zebra finch) (Poephila guttata) Putative biphenyl hydrolase-like protein variant 1 | Taeniopygia guttata |
| takru-h2sci9 | Takifugu rubripes (Japanese pufferfish) (Fugu rubripes) Uncharacterized protein | Takifugu rubripes |
| tetng-q4s6r1 | Tetraodon nigroviridis (Spotted green pufferfish) (Chelonodon nigroviridis) hypothetical protein (fragment) | Tetraodon nigroviridis |
| triad-b3rty7 | Trichoplax adhaerens (Trichoplax reptans) Putative uncharacterized protein | Trichoplax adhaerens |
| triad-b3rur2 | Trichoplax adhaerens (Trichoplax reptans) Putative uncharacterized protein | Trichoplax adhaerens |
| triad-b3rwr4 | Trichoplax adhaerens (Trichoplax reptans) Putative uncharacterized protein | Trichoplax adhaerens |
| triad-b3s3d8 | Trichoplax adhaerens (Trichoplax reptans) Putative uncharacterized protein | Trichoplax adhaerens |
| triad-b3seb0 | Trichoplax adhaerens (Trichoplax reptans) Putative uncharacterized protein | Trichoplax adhaerens |
| triad-b3seb1 | Trichoplax adhaerens (Trichoplax reptans) Putative uncharacterized protein | Trichoplax adhaerens |
| trica-d6w9c0 | Tribolium castaneum (Red flour beetle) Putative uncharacterized protein | Tribolium castaneum |
| xenla-q3kps5 | Xenopus laevis (African clawed frog) hypothetical protein | Xenopus laevis |
| xentr-f7acc5 | Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) Uncharacterized protein | Xenopus tropicalis |
| Gene_locus_frgt | Name | Species |
|---|---|---|
| ampqe-i1e578 | Amphimedon queenslandica (Sponge) Uncharacterized protein | Amphimedon queenslandica |
| camfo-e2aqx5.1 | Camponotus floridanus (Florida carpenter ant) Valacyclovir hydrolase | Camponotus floridanus |
| camfo-e2aqx5.2 | Camponotus floridanus (Florida carpenter ant) Valacyclovir hydrolase | Camponotus floridanus |
| danpl-g6di47 | Danaus plexippus (Monarch butterfly) Uncharacterized protein | Danaus plexippus |
| hetga-g5bke7 | Heterocephalus glaber (Naked mole rat) Valacyclovir hydrolase | Heterocephalus glaber |
| nemve-a7rfc4 | Nematostella vectensis (Starlet sea anemone) Predicted protein | Nematostella vectensis |
| ornan-f7ckq8 | Ornithorhynchus anatinus (Duckbill platypus) Uncharacterized protein | Ornithorhynchus anatinus |
| rhisa-c9w188 | Rhipicephalus sanguineus (Brown dog tick) (Ixodes sanguineus) Hypothetical secreted protein | Rhipicephalus sanguineus |
| sarha-g3wn21 | Sarcophilus harrisii (Tasmanian devil) (Sarcophilus laniarius) Uncharacterized protein | Sarcophilus harrisii |
| Substrate | Chemical Nomenclature | Proteins |
|---|---|---|
| Homocysteine-thiolactone | (3S)-3-aminothiolan-2-one | human-BPHL human-CES1 human-BCHE |
| Valacyclovir | 2-[(2-amino-6-oxo-3H-purin-9-yl)methoxy]ethyl (2S)-2-amino-3-methylbutanoate || 2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]ethyl (2S)-2-amino-3-methylbutanoate | human-BPHL mouse-bphl |
| Valgancyclovir | [2-[(2-amino-6-oxo-3H-purin-9-yl)methoxy]-3-hydroxypropyl] (2S)-2-amino-3-methylbutanoate | human-BPHL mouse-bphl |
| Inhibitor | Chemical Nomenclature | Proteins |
|---|---|---|
| Tyrosinamide | [(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]azanium | human-BPHL |
References (8)
| Title : Effect of biphenyl hydrolase-like (BPHL) gene disruption on the intestinal stability, permeability and absorption of valacyclovir in wildtype and Bphl knockout mice - Hu_2018_Biochem.Pharmacol_156_147 |
| Author(s) : Hu Y , Epling D , Shi J , Song F , Tsume Y , Zhu HJ , Amidon GL , Smith DE |
| Ref : Biochemical Pharmacology , 156 :147 , 2018 |
| Abstract : |
| PubMedSearch : Hu_2018_Biochem.Pharmacol_156_147 |
| PubMedID: 30121252 |
| Gene_locus related to this paper: human-BPHL |
| Title : Specificity of a prodrug-activating enzyme hVACVase: the leaving group effect - Sun_2010_Mol.Pharm_7_2362 |
| Author(s) : Sun J , Dahan A , Walls ZF , Lai L , Lee KD , Amidon GL |
| Ref : Mol Pharm , 7 :2362 , 2010 |
| Abstract : |
| PubMedSearch : Sun_2010_Mol.Pharm_7_2362 |
| PubMedID: 21028903 |
| Gene_locus related to this paper: human-BPHL |
| Title : Molecular basis of prodrug activation by human valacyclovirase, an alpha-amino acid ester hydrolase - Lai_2008_J.Biol.Chem_283_9318 |
| Author(s) : Lai L , Xu Z , Zhou J , Lee KD , Amidon GL |
| Ref : Journal of Biological Chemistry , 283 :9318 , 2008 |
| Abstract : |
| PubMedSearch : Lai_2008_J.Biol.Chem_283_9318 |
| PubMedID: 18256025 |
| Gene_locus related to this paper: human-BPHL |
| Title : A novel nucleoside prodrug-activating enzyme: substrate specificity of biphenyl hydrolase-like protein - Kim_2004_Mol.Pharm_1_117 |
| Author(s) : Kim I , Song X , Vig BS , Mittal S , Shin HC , Lorenzi PJ , Amidon GL |
| Ref : Mol Pharm , 1 :117 , 2004 |
| Abstract : |
| PubMedSearch : Kim_2004_Mol.Pharm_1_117 |
| PubMedID: 15832508 |
| Gene_locus related to this paper: human-BPHL |
| Title : Identification of a human valacyclovirase: biphenyl hydrolase-like protein as valacyclovir hydrolase - Kim_2003_J.Biol.Chem_278_25348 |
| Author(s) : Kim I , Chu XY , Kim S , Provoda CJ , Lee KD , Amidon GL |
| Ref : Journal of Biological Chemistry , 278 :25348 , 2003 |
| Abstract : |
| PubMedSearch : Kim_2003_J.Biol.Chem_278_25348 |
| PubMedID: 12732646 |
| Gene_locus related to this paper: human-BPHL |
| Title : Structural characterization and chromosomal localization of the gene encoding human biphenyl hydrolase-related protein (BPHL) - Puente_1998_Genomics_51_459 |
| Author(s) : Puente XS , Pendas AM , Lopez-Otin C |
| Ref : Genomics , 51 :459 , 1998 |
| Abstract : |
| PubMedSearch : Puente_1998_Genomics_51_459 |
| PubMedID: 9721218 |
| Gene_locus related to this paper: human-BPHL |
| Title : Cloning and expression analysis of a novel human serine hydrolase with sequence similarity to prokaryotic enzymes involved in the degradation of aromatic compounds - Puente_1995_J.Biol.Chem_270_12926 |
| Author(s) : Puente XS , Lopez-Otin C |
| Ref : Journal of Biological Chemistry , 270 :12926 , 1995 |
| Abstract : |
| PubMedSearch : Puente_1995_J.Biol.Chem_270_12926 |
| PubMedID: 7759552 |
| Gene_locus related to this paper: human-BPHL |
| Title : Cloning and sequencing of a complementary DNA encoding a Mr 70,000 human breast epithelial mucin-associated antigen - Larocca_1990_Cancer.Res_50_5925 |
| Author(s) : Larocca D , Peterson JA , Walkup G , Urrea R , Ceriani RL |
| Ref : Cancer Research , 50 :5925 , 1990 |
| Abstract : |
| PubMedSearch : Larocca_1990_Cancer.Res_50_5925 |
| PubMedID: 2393862 |
| Gene_locus related to this paper: human-BPHL |