1c3v
From Proteopedia
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|GENE= | |GENE= | ||
|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam05173 DapB_C], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam01113 DapB_N]</span> | |DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam05173 DapB_C], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam01113 DapB_N]</span> | ||
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c3v OCA], [http://www.ebi.ac.uk/pdbsum/1c3v PDBsum | + | |RELATEDENTRY=[[1pl9|1PL9]] |
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c3v OCA], [http://www.ebi.ac.uk/pdbsum/1c3v PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1c3v RCSB]</span> | ||
}} | }} | ||
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[[Category: two-domain structure]] | [[Category: two-domain structure]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:14:00 2008'' |
Revision as of 16:14, 30 March 2008
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| , resolution 2.39Å | |||||||
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| Ligands: | , , | ||||||
| Activity: | Dihydrodipicolinate reductase, with EC number 1.3.1.26 | ||||||
| Domains: | DapB_C, DapB_N | ||||||
| Related: | 1PL9
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
DIHYDRODIPICOLINATE REDUCTASE FROM MYCOBACTERIUM TUBERCULOSIS COMPLEXED WITH NADPH AND PDC
Overview
Dihydrodipicolinate reductase (DHPR) catalyzes the reduced pyridine nucleotide-dependent reduction of the alpha,beta-unsaturated cyclic imine, dihydrodipicolinate, to generate tetrahydrodipicolinate. This enzyme catalyzes the second step in the bacterial biosynthetic pathway that generates meso-diaminopimelate, a component of bacterial cell walls, and the amino acid L-lysine. The Mycobacterium tuberculosis dapB-encoded DHPR has been cloned, expressed, purified, and crystallized in two ternary complexes with NADH or NADPH and the inhibitor 2,6-pyridinedicarboxylate (2,6-PDC). The structures have been solved using molecular replacement strategies, and the DHPR-NADH-2,6-PDC and DHPR-NADPH-2,6-PDC complexes have been refined against data to 2.3 and 2.5 A, respectively. The M. tuberculosis DHPR is a tetramer of identical subunits, with each subunit composed of two domains connected by two flexible hinge regions. The N-terminal domain binds pyridine nucleotide, while the C-terminal domain is involved in both tetramer formation and substrate/inhibitor binding. The M. tuberculosis DHPR uses NADH and NADPH with nearly equal efficiency based on V/K values. To probe the nature of this substrate specificity, we have generated two mutants, K9A and K11A, residues that are close to the 2'-phosphate of NADPH. These two mutants exhibit decreased specificity for NADPH by factors of 6- and 30-fold, respectively, but the K11A mutant exhibits 270% of WT activity using NADH. The highly conserved structure of the nucleotide fold may permit other enzyme's nucleotide specificity to be altered using similar mutagenic strategies.
About this Structure
1C3V is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
The three-dimensional structures of the Mycobacterium tuberculosis dihydrodipicolinate reductase-NADH-2,6-PDC and -NADPH-2,6-PDC complexes. Structural and mutagenic analysis of relaxed nucleotide specificity., Cirilli M, Zheng R, Scapin G, Blanchard JS, Biochemistry. 2003 Sep 16;42(36):10644-50. PMID:12962488
Page seeded by OCA on Sun Mar 30 19:14:00 2008
Categories: Dihydrodipicolinate reductase | Mycobacterium tuberculosis | Single protein | Blanchard, J S. | Cirilli, M. | Scapin, G. | TBSGC, TB Structural Genomics Consortium. | Zheng, R. | Protein structure initiative | Psi | Structural genomic | Tb structural genomics consortium | Tbsgc | Two-domain structure
