2.02012-05-31 14:33:04 -06002015-06-03 17:19:32 -0600ECMDB20205M2MDB001051UDP-N-Acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanineUDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine is a member of the chemical class known as Peptides. These are compounds containing an amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another. UDP-MurNAc-pentapeptide is a peptidoglycan precursor. It is a key component of peptidoglycan synthesis. The peptidoglycan synthesis pathway starts at the cytoplasm, where in six steps the peptidoglycan precursor a UDP-N-acetylmuramoyl-pentapeptide is synthesized. This precursor is then attached to the memberane acceptor all-trans-undecaprenyl phosphate, generating a N-acetylmuramoyl-pentapeptide-diphosphoundecaprenol, also known as lipid I. Another transferase then adds UDP-N-acetyl-alpha-D-glucosamine, yielding the complete monomeric unit a lipid , also known as lipid . This final lipid intermediate is transferred through the membrane. The peptidoglycan monomers are then polymerized on the outside surface by glycosyltransferases, which form the linear glycan chains, and transpeptidases, which catalyze the formation of peptide crosslinks. UDP-MurNAc-pentapeptide is a feedback inhibitor of UDP-MurNAc-peptide synthesis. (PMID 357424)UDP-Mur2Ac(oyl-L-Ala-g-D-Glu-L-Lys-D-Ala-D-Ala)UDP-MurNAc-pentapeptideUDP-N-Acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanineUDP-N-Acetylmuramoyl-L-alanyl-g-D-glutamyl-L-lysyl-D-alanyl-D-alanineUDP-N-Acetylmuramoyl-L-alanyl-gamma-D-glutamyl-L-lysyl-D-alanyl-D-alanineUDP-N-Acetylmuramoyl-L-alanyl-γ-D-glutamyl-L-lysyl-D-alanyl-D-alanineUdpmurac(oyl-L-ala-D-g-glu-L-lys-D-ala-D-ala)Udpmurac(oyl-L-ala-D-gamma-glu-L-LYS-D-ala-D-ala)Udpmurac(oyl-L-ala-D-γ-glu-L-lys-D-ala-D-ala)C40H65N9O26P21149.93631149.3515963214-{[(1S)-5-amino-1-{[(1R)-1-{[(1R)-1-carboxyethyl]-C-hydroxycarbonimidoyl}ethyl]-C-hydroxycarbonimidoyl}pentyl]-C-hydroxycarbonimidoyl}-2-{[(2S)-2-[(2-{[(3R,4R,5S,6R)-2-({[({[(2R,3S,4R,5R)-3,4-dihydroxy-5-(4-hydroxy-2-oxo-1,2-dihydropyrimidin-1-yl)oxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)-5-hydroxy-3-[(1-hydroxyethylidene)amino]-6-(hydroxymethyl)oxan-4-yl]oxy}-1-hydroxypropylidene)amino]-1-hydroxypropylidene]amino}butanoic acid4-{[(1S)-5-amino-1-{[(1R)-1-{[(1R)-1-carboxyethyl]-C-hydroxycarbonimidoyl}ethyl]-C-hydroxycarbonimidoyl}pentyl]-C-hydroxycarbonimidoyl}-2-{[(2S)-2-[(2-{[(3R,4R,5S,6R)-2-[({[(2R,3S,4R,5R)-3,4-dihydroxy-5-(4-hydroxy-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy(hydroxy)phosphoryl}oxy(hydroxy)phosphoryl)oxy]-5-hydroxy-3-[(1-hydroxyethylidene)amino]-6-(hydroxymethyl)oxan-4-yl]oxy}-1-hydroxypropylidene)amino]-1-hydroxypropylidene]amino}butanoic acid[H]C(C)(O[C@@]1([H])[C@]([H])(O)[C@@]([H])(CO)OC([H])(OP(O)(=O)OP(O)(=O)OC[C@@]2([H])O[C@@]([H])(N3C=CC(O)=NC3=O)[C@]([H])(O)[C@]2([H])O)[C@]1([H])N=C(C)O)C(O)=N[C@@]([H])(C)C(O)=NC([H])(CCC(O)=N[C@@]([H])(CCCCN)C(O)=N[C@]([H])(C)C(O)=N[C@]([H])(C)C(O)=O)C(O)=OInChI=1S/C40H65N9O26P2/c1-16(32(57)44-18(3)37(61)62)43-35(60)21(8-6-7-12-41)46-25(52)10-9-22(38(63)64)47-33(58)17(2)42-34(59)19(4)71-31-27(45-20(5)51)39(73-23(14-50)29(31)55)74-77(68,69)75-76(66,67)70-15-24-28(54)30(56)36(72-24)49-13-11-26(53)48-40(49)65/h11,13,16-19,21-24,27-31,36,39,50,54-56H,6-10,12,14-15,41H2,1-5H3,(H,42,59)(H,43,60)(H,44,57)(H,45,51)(H,46,52)(H,47,58)(H,61,62)(H,63,64)(H,66,67)(H,68,69)(H,48,53,65)/t16-,17+,18-,19?,21+,22?,23-,24-,27-,28-,29-,30-,31-,36-,39?/m1/s1PFMVORMCVGOQKR-FQSOPKRZSA-NCytoplasmPeriplasmlogp-0.38logs-3.75solubility2.05e-01 g/llogp-3.7pka_strongest_acidic1.71pka_strongest_basic10.21iupac4-{[(1S)-5-amino-1-{[(1R)-1-{[(1R)-1-carboxyethyl]-C-hydroxycarbonimidoyl}ethyl]-C-hydroxycarbonimidoyl}pentyl]-C-hydroxycarbonimidoyl}-2-{[(2S)-2-[(2-{[(3R,4R,5S,6R)-2-({[({[(2R,3S,4R,5R)-3,4-dihydroxy-5-(4-hydroxy-2-oxo-1,2-dihydropyrimidin-1-yl)oxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)-5-hydroxy-3-[(1-hydroxyethylidene)amino]-6-(hydroxymethyl)oxan-4-yl]oxy}-1-hydroxypropylidene)amino]-1-hydroxypropylidene]amino}butanoic acidaverage_mass1149.9363mono_mass1149.351596321smiles[H]C(C)(O[C@@]1([H])[C@]([H])(O)[C@@]([H])(CO)OC([H])(OP(O)(=O)OP(O)(=O)OC[C@@]2([H])O[C@@]([H])(N3C=CC(O)=NC3=O)[C@]([H])(O)[C@]2([H])O)[C@]1([H])N=C(C)O)C(O)=N[C@@]([H])(C)C(O)=NC([H])(CCC(O)=N[C@@]([H])(CCCCN)C(O)=N[C@]([H])(C)C(O)=N[C@]([H])(C)C(O)=O)C(O)=OformulaC40H65N9O26P2inchiInChI=1S/C40H65N9O26P2/c1-16(32(57)44-18(3)37(61)62)43-35(60)21(8-6-7-12-41)46-25(52)10-9-22(38(63)64)47-33(58)17(2)42-34(59)19(4)71-31-27(45-20(5)51)39(73-23(14-50)29(31)55)74-77(68,69)75-76(66,67)70-15-24-28(54)30(56)36(72-24)49-13-11-26(53)48-40(49)65/h11,13,16-19,21-24,27-31,36,39,50,54-56H,6-10,12,14-15,41H2,1-5H3,(H,42,59)(H,43,60)(H,44,57)(H,45,51)(H,46,52)(H,47,58)(H,61,62)(H,63,64)(H,66,67)(H,68,69)(H,48,53,65)/t16-,17+,18-,19?,21+,22?,23-,24-,27-,28-,29-,30-,31-,36-,39?/m1/s1inchikeyPFMVORMCVGOQKR-FQSOPKRZSA-Npolar_surface_area559.96refractivity250.93polarizability106.12rotatable_bond_count30acceptor_count31donor_count16physiological_charge-3formal_charge0Lysine biosynthesisLysine is biosynthesized from L-aspartic acid. L-aspartic acid can be incorporated into the cell through various methods: C4 dicarboxylate / orotate:H+ symporter ,
glutamate / aspartate : H+ symporter GltP, dicarboxylate transporter , C4 dicarboxylate / C4 monocarboxylate transporter DauA, glutamate / aspartate ABC transporter
L-aspartic acid is phosphorylated by an ATP-driven Aspartate kinase resulting in ADP and L-aspartyl-4-phosphate. L-aspartyl-4-phosphate is then dehydrogenated through an NADPH driven aspartate semialdehyde dehydrogenase resulting in a release of phosphate, NADP and L-aspartic 4-semialdehyde (involved in methionine biosynthesis).
L-aspartic 4-semialdehyde interacts with a pyruvic acid through a 4-hydroxy-tetrahydrodipicolinate synthase resulting in a release of hydrogen ion, water and
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate. The latter compound is then reduced by an NADPH driven 4-hydroxy-tetrahydrodipicolinate reductase resulting in a release of water, NADP and (S)-2,3,4,5-tetrahydrodipicolinate, This compound interacts with succinyl-CoA and water through a tetrahydrodipicolinate succinylase resulting in a release of coenzyme A and N-Succinyl-2-amino-6-ketopimelate. This compound interacts with L-glutamic acid through a N-succinyldiaminopimelate aminotransferase resulting in oxoglutaric acid, N-succinyl-L,L-2,6-diaminopimelate. The latter compound is then desuccinylated by reacting with water through a N-succinyl-L-diaminopimelate desuccinylase resulting in a succinic acid and L,L-diaminopimelate. This compound is then isomerized through a diaminopimelate epimerase resulting in a meso-diaminopimelate (involved in peptidoglyccan biosynthesis I). This compound is then decarboxylated by a diaminopimelate decarboxylase resulting in a release of carbon dioxide and L-lysine.
L-lysine is then incorporated into lysine degradation pathway. Lysine also regulate its own biosynthesis by repressing dihydrodipicolinate synthase and also repressing lysine-sensitive aspartokinase 3.
A metabolic connection joins synthesis of an amino acid, lysine, to synthesis of cell wall material. Diaminopimelate is a precursor both for lysine and for cell wall components. The synthesis of lysine, methionine and threonine share two reactions at the start of the three pathways, the reactions converting L-aspartate to L-aspartate semialdehyde. The reaction involving aspartate kinase is carried out by three isozymes, one specific for synthesis of each end product amino acid. Each of the three aspartate kinase isozymes is regulated by its corresponding end product amino acid.PW000771ec00300MetabolicPeptidoglycan biosynthesisec00550Metabolic pathwayseco01100Specdb::NmrOneD294755Specdb::NmrOneD294756Specdb::NmrOneD294757Specdb::NmrOneD294758Specdb::NmrOneD294759Specdb::NmrOneD294760Specdb::NmrOneD294761Specdb::NmrOneD294762Specdb::NmrOneD294763Specdb::NmrOneD294764Specdb::NmrOneD294765Specdb::NmrOneD294766Specdb::NmrOneD294767Specdb::NmrOneD294768Specdb::NmrOneD294769Specdb::NmrOneD294770Specdb::NmrOneD294771Specdb::NmrOneD294772Specdb::NmrOneD294773Specdb::NmrOneD294774Specdb::MsMs27140Specdb::MsMs27141Specdb::MsMs27142Specdb::MsMs33698Specdb::MsMs33699Specdb::MsMs33700440448389383C0470217277C3Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114.22080510van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25.17765195Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948.18331064Ishiguro, E. E., Ramey, W. D. (1978). "Involvement of the relA gene product and feedback inhibition in the regulation of DUP-N-acetylmuramyl-peptide synthesis in Escherichia coli." J Bacteriol 135:766-774.357424Phospho-N-acetylmuramoyl-pentapeptide-transferaseP0A6W3MRAY_ECOLImraYhttp://ecmdb.ca/proteins/P0A6W3.xmlUDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligaseP11880MURF_ECOLImurFhttp://ecmdb.ca/proteins/P11880.xmlAdenosine triphosphate + UDP-N-Acetylmuramoyl-L-alanyl-gamma-D-glutamyl-L-lysine + D-Alanyl-D-alanine <> ADP + Phosphate + UDP-N-Acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanineR04573UDP-N-Acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine + Di-trans,poly-cis-undecaprenyl phosphate + UDP-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala) <> Uridine 5'-monophosphate + MurAc(oyl-L-Ala-D-gamma-Glu-L-Lys-D-Ala-D-Ala)-diphospho-undecaprenol + Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)-diphosphoundecaprenolR05629Adenosine triphosphate + UDP-N-Acetylmuramoyl-L-alanyl-gamma-D-glutamyl-L-lysine + D-Alanyl-D-alanine > ADP + Inorganic phosphate + UDP-N-Acetylmuramoyl-L-alanyl-D-glutamyl-L-lysyl-D-alanyl-D-alanine