Abstract
The molecular structure of the D-alanine:D-alanine ligase of the ddlB gene of Escherichia coli , co-crystallized with an S , R -methylphosphinate and adenosine triphosphate, was determined by x-ray diffraction to a resolution of 2.3 angstroms. A catalytic mechanism for the ligation of two D-alanine substrates is proposed in which a helix dipole and a hydrogen-bonded triad of tyrosine, serine, and glutamic acid assist binding and deprotonation steps. From sequence comparison, it is proposed that a different triad exists in a recently discovered D-alanine:D-lactate ligase (VanA) present in vancomycin-resistant enterococci. A molecular mechanism for the altered specificity of VanA is suggested.
References
34
Referenced
192
-
ARTHUR, M, GENETICS AND MECHANISMS OF GLYCOPEPTIDE RESISTANCE IN ENTEROCOCCI, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 37: 1563 (1993).
(
10.1128/AAC.37.8.1563
) / ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (1993) - Brunger A. T. X-PLOR Manual Version 2.1 (1990).
10.1021/bi00107a007
-
CARSON, M, RIBBON MODELS OF MACROMOLECULES, JOURNAL OF MOLECULAR GRAPHICS 5: 103 (1987).
(
10.1016/0263-7855(87)80010-3
) / JOURNAL OF MOLECULAR GRAPHICS (1987) 10.1126/science.8153624
-
DUTKAMALEN, S, SEQUENCE OF THE VANC GENE OF ENTEROCOCCUS-GALLINARUM BM4174 ENCODING A D-ALANINE - D-ALANINE LIGASE-RELATED PROTEIN NECESSARY FOR VANCOMYCIN RESISTANCE, GENE 112: 53 (1992).
(
10.1016/0378-1119(92)90302-6
) / GENE (1992) -
DUTKAMALEN, S, THE VANA GLYCOPEPTIDE RESISTANCE PROTEIN IS RELATED TO D-ALANYL-D-ALANINE LIGASE CELL-WALL BIOSYNTHESIS ENZYMES, MOLECULAR & GENERAL GENETICS 224: 364 (1990).
(
10.1007/BF00262430
) / MOLECULAR & GENERAL GENETICS (1990) - Frere, J.-M., The Chemistry of β-Lactams: 148 (1992). / The Chemistry of β-Lactams (1992)
- FUREY, W, AM CRYSTALLOGR ASS SOC ABSTR 18: 73 (1990). / AM CRYSTALLOGR ASS SOC ABSTR (1990)
-
HAMMES, W.P., PHARMACOL THERAPEUT 14: 265 (1981).
(
10.1016/0163-7258(81)90030-9
) / PHARMACOL THERAPEUT (1981) -
HOWARD, A.J., THE USE OF AN IMAGING PROPORTIONAL COUNTER IN MACROMOLECULAR CRYSTALLOGRAPHY, JOURNAL OF APPLIED CRYSTALLOGRAPHY 20: 383 (1987).
(
10.1107/S0021889887086436
) / JOURNAL OF APPLIED CRYSTALLOGRAPHY (1987) - Sack, J. S., Journal of Molecular Graphics 6: 224 (1988). / Journal of Molecular Graphics (1988)
-
JONES, T.A., INTERACTIVE COMPUTER-GRAPHICS - FRODO, METHODS IN ENZYMOLOGY 115: 157 (1985).
(
10.1016/0076-6879(85)15014-7
) / METHODS IN ENZYMOLOGY (1985) -
KONNERT, J.H., A RESTRAINED-PARAMETER THERMAL-FACTOR REFINEMENT PROCEDURE, ACTA CRYSTALLOGRAPHICA SECTION A 36: 344 (1980).
(
10.1107/S0567739480000794
) / ACTA CRYSTALLOGRAPHICA SECTION A (1980) -
MCDERMOTT, A.E., ROTATIONAL RESONANCE DETERMINATION OF THE STRUCTURE OF AN ENZYME-INHIBITOR COMPLEX - PHOSPHORYLATION OF AN (AMINOALKYL)PHOSPHINATE INHIBITOR OF D-ALANYL-D-ALANINE LIGASE BY ATP, BIOCHEMISTRY 29: 5767 (1990).
(
10.1021/bi00476a018
) / BIOCHEMISTRY (1990) 10.1126/science.257.5073.1064
-
NEUHAUS, F.C., ENZYMATIC SYNTHESIS OF D-ALANYL-D-ALANINE .3. ON INHIBITION OF D-ALANYL-D-ALANINE SYNTHETASE BY ANTIBIOTIC D-CYCLOSERINE, BIOCHEMISTRY 3: 471 (1964).
(
10.1021/bi00892a001
) / BIOCHEMISTRY (1964) -
NEUHAUS, F.C., ENZYMATIC SYNTHESIS OF D-ALANYL-D-ALANINE .1. PURIFICATION AND PROPERTIES OF D-ALANYL-D-ALANINE SYNTHETASE, JOURNAL OF BIOLOGICAL CHEMISTRY 237: 778 (1962).
(
10.1016/S0021-9258(18)60372-2
) / JOURNAL OF BIOLOGICAL CHEMISTRY (1962) -
NEUHAUS, F.C., ENZYMATIC SYNTHESIS OF D-ALANYL-D-ALANINE .2. KINETIC STUDIES ON D-ALANYL-D-ALANINE SYNTHETASE, JOURNAL OF BIOLOGICAL CHEMISTRY 237: 3128 (1962).
(
10.1016/S0021-9258(18)50132-0
) / JOURNAL OF BIOLOGICAL CHEMISTRY (1962) -
PARSONS, W.H., PHOSPHINIC ACID INHIBITORS OF D-ALANYL-D-ALANINE LIGASE, JOURNAL OF MEDICINAL CHEMISTRY 31: 1772 (1988).
(
10.1021/jm00117a017
) / JOURNAL OF MEDICINAL CHEMISTRY (1988) -
REYNOLDS, P.E., ANALYSIS OF PEPTIDOGLYCAN PRECURSORS IN VANCOMYCIN-RESISTANT ENTEROCOCCUS-GALLINARUM BM4174, BIOCHEMICAL JOURNAL 301: 5 (1994).
(
10.1042/bj3010005
) / BIOCHEMICAL JOURNAL (1994) -
SARASTE, M, THE P-LOOP - A COMMON MOTIF IN ATP-BINDING AND GTP-BINDING PROTEINS, TRENDS IN BIOCHEMICAL SCIENCES 15: 430 (1990).
(
10.1016/0968-0004(90)90281-F
) / TRENDS IN BIOCHEMICAL SCIENCES (1990) 10.1126/science.8153626
-
STROMINGER, J.L., COMPETITIVE INHIBITION OF ENZYMATIC REACTIONS BY OXAMYCIN, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 82: 998 (1960).
(
10.1021/ja01489a058
) / JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (1960) -
TANAKA, T, FLEXIBILITY IMPAIRED BY MUTATIONS REVEALED THE MULTIFUNCTIONAL ROLES OF THE LOOP IN GLUTATHIONE SYNTHETASE, BIOCHEMISTRY 32: 12398 (1993).
(
10.1021/bi00097a018
) / BIOCHEMISTRY (1993) 10.1126/science.8153616
- Waley, S. G., The Chemistry of β-Lactams: 198 (1992). / The Chemistry of β-Lactams (1992)
-
WALSH, C.T., ENZYMES IN THE D-ALANINE BRANCH OF BACTERIAL-CELL WALL PEPTIDOGLYCAN ASSEMBLY, JOURNAL OF BIOLOGICAL CHEMISTRY 264: 2393 (1989).
(
10.1016/S0021-9258(19)81624-1
) / JOURNAL OF BIOLOGICAL CHEMISTRY (1989) 10.1126/science.8392747
- WALSH C.T. unpublished data.
-
WRIGHT, G.D., D-ALANYL-D-ALANINE LIGASES AND THE MOLECULAR MECHANISM OF VANCOMYCIN RESISTANCE, ACCOUNTS OF CHEMICAL RESEARCH 25: 468 (1992).
(
10.1021/ar00022a006
) / ACCOUNTS OF CHEMICAL RESEARCH (1992) -
WRIGHT, G.D., IDENTIFICATION OF A COMMON PROTEASE-SENSITIVE REGION IN D-ALANYL-D-ALANINE AND D-ALANYL-D-LACTATE LIGASES AND PHOTOAFFINITY-LABELING WITH 8-AZIDO ATP, PROTEIN SCIENCE 2: 1765 (1993).
(
10.1002/pro.5560021020
) / PROTEIN SCIENCE (1993) -
YAMAGUCHI, H, 3-DIMENSIONAL STRUCTURE OF THE GLUTATHIONE SYNTHETASE FROM ESCHERICHIA-COLI-B AT 2.O-ANGSTROM RESOLUTION, JOURNAL OF MOLECULAR BIOLOGY 229: 1083 (1993).
(
10.1006/jmbi.1993.1106
) / JOURNAL OF MOLECULAR BIOLOGY (1993) -
ZAWADZKE, L.E., EXISTENCE OF 2 D-ALANINE - D-ALANINE LIGASES IN ESCHERICHIA-COLI - CLONING AND SEQUENCING OF THE DDLA GENE AND PURIFICATION AND CHARACTERIZATION OF THE DDLA AND DDLB ENZYMES, BIOCHEMISTRY 30: 1673 (1991).
(
10.1021/bi00220a033
) / BIOCHEMISTRY (1991)
Dates
Type | When |
---|---|
Created | 18 years, 10 months ago (Oct. 5, 2006, 8:01 p.m.) |
Deposited | 1 year, 7 months ago (Jan. 14, 2024, 11:17 p.m.) |
Indexed | 1 month, 1 week ago (July 11, 2025, 9:05 p.m.) |
Issued | 30 years, 10 months ago (Oct. 21, 1994) |
Published | 30 years, 10 months ago (Oct. 21, 1994) |
Published Print | 30 years, 10 months ago (Oct. 21, 1994) |
@article{Fan_1994, title={Vancomycin Resistance: Structure of D-Alanine:D-Alanine Ligase at 2.3 Å Resolution}, volume={266}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.7939684}, DOI={10.1126/science.7939684}, number={5184}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Fan, Chang and Moews, Paul C. and Walsh, Christopher T. and Knox, James R.}, year={1994}, month=oct, pages={439–443} }