Dihydrodipicolinate synthase: Difference between revisions

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<StructureSection load='V9da1.pdb' size="400" color="" frame="true"  spin="on" Scene='2v9d/Tetramer/1' align="right" caption= >
<StructureSection load='2v9d' size='350' side='right' caption='Structure of Se-Met dihydrodipicolinate synthase (PDB entry [[2v9d]])' scene=''>
[[Image:2v9d.jpg|left|200px]]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


'''CRYSTAL STRUCTURE OF YAGE, A PROPHAGE PROTEIN BELONGING TO THE DIHYDRODIPICOLINIC ACID SYNTHASE FAMILY FROM ''E. COLI K12'''''<br />
'''CRYSTAL STRUCTURE OF YAGE, A PROPHAGE PROTEIN BELONGING TO THE DIHYDRODIPICOLINIC ACID SYNTHASE FAMILY FROM ''E. COLI K12'''''<br />




One approach of the incorporation of genetic material from different species into bacterial genomes is infection by a bacteriophage. The ''yagE'' gene is located in the ''E. coli K12'' genome and it is part of prophage ''CP4-6'' encoding a 33-kDa putative dihydrodipicolinate synthase (DHDPS)-like protein (UniProtKB/Swiss-prot: [http://www.expasy.org/uniprot/P75682 P75682]). This DHDPS-like domain is a member of the N-acetyl neuraminate lyase (NAL) subfamily comprises an 8-fold <scene name='2v9d/Alpha_beta/2'>α/β-barrel</scene> ([http://en.wikipedia.org/wiki/TIM_barrel TIM barrel]) with a small C-terminal α-helical domain (Inter pro: [http://www.ebi.ac.uk/interpro/ISearch?query=IPR005263 IPR005263]). Many enzymes possess this DHDPS domain (''e.g.'' HBPHA, KDGA, NAL, DOGDH, and DHDPS). All these enzymes contain an 8-fold α/β barrel and a small C-terminal α-helical region. <scene name='2v8z/Comparison/2'>Comparison</scene> between <font color='red'><b>orthorhombic</b></font> ([[2v8z]]) and <font color='cyan'><b>monoclinic</b></font> ([[2v9d]]) crystal forms of YagE revealed striking similarity.   
One approach of the incorporation of genetic material from different species into bacterial genomes is infection by a bacteriophage. The ''yagE'' gene is located in the ''E. coli K12'' genome and it is part of prophage ''CP4-6'' encoding a 33-kDa putative '''dihydrodipicolinate synthase''' or  '''4-hydroxy-tetrahydrodihydrodipicolinate synthase''' (DHDPS)-like protein (UniProtKB/Swiss-prot: [http://www.expasy.org/uniprot/P75682 P75682]). This DHDPS-like domain is a member of the N-acetyl neuraminate lyase (NAL) subfamily comprises an 8-fold <scene name='2v9d/Alpha_beta/2'>α/β-barrel</scene> ([http://en.wikipedia.org/wiki/TIM_barrel TIM barrel]) with a small C-terminal α-helical domain (Inter pro: [http://www.ebi.ac.uk/interpro/ISearch?query=IPR005263 IPR005263]). Many enzymes possess this DHDPS domain (''e.g.'' HBPHA, KDGA, NAL, DOGDH, and DHDPS). All these enzymes contain an 8-fold α/β barrel and a small C-terminal α-helical region. <scene name='2v8z/Comparison/2'>Comparison</scene> between <font color='red'><b>orthorhombic</b></font> ([[2v8z]]) and <font color='cyan'><b>monoclinic</b></font> ([[2v9d]]) crystal forms of YagE revealed striking similarity.   
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Members of the NAL protein subfamily have very similar active sites and a single amino acid substitution can significantly change their function. For example, NAL ([[1nal]]) gets DHDPS activity by substitution of a <scene name='2v9d/Leucine142/2'>leucine</scene> <font color='orange'><b>(orange)</b></font> to <scene name='2v9d/Arginine142/2'>arginine</scene> <font color='blue'><b>(blue)</b></font> at position 142. The possible active site region of <font color='cyan'><b>YagE</b></font> demonstrates closest sequence similarity to the active site of <font color='magenta'><b>KDG aldolase of SsKDGA</b></font> ([[1w3i]]) and <font color='black'><b>NAL of EcNAL</b></font> ([[1nal]]) (yellow), suggesting that this protein can perform either of these functions. Although the active site of EcDHDPS ([[1xky]]) and BaDHDPS ([[2ats]]) shows similarities, the important residue that differentiates between NAL and DHDPS, namely Leu142 (in [[1nal]]), is also present in YagE <scene name='2v9d/Leucine150/2'>(Leu150)</scene> <font color='cyan'><b>(labeled cyan)</b></font> at that particular position suggesting that YagE performs a NAL-related function rather than DHDPS-related one. In conclusion, the high-resolution X-ray structure of YagE provides a clue that it probably belongs to the NAL subfamily of proteins. Although the exact molecular function of YagE is still unknown, its structure provides a handle for understanding its molecular function based on knowledge about conserved residues of the putative active site.  
Members of the NAL protein subfamily have very similar active sites and a single amino acid substitution can significantly change their function. For example, NAL ([[1nal]]) gets DHDPS activity by substitution of a <scene name='2v9d/Leucine142/2'>leucine</scene> <font color='orange'><b>(orange)</b></font> to <scene name='2v9d/Arginine142/2'>arginine</scene> <font color='blue'><b>(blue)</b></font> at position 142. The possible active site region of <font color='cyan'><b>YagE</b></font> demonstrates closest sequence similarity to the active site of <font color='magenta'><b>KDG aldolase of SsKDGA</b></font> ([[1w3i]]) and <font color='black'><b>NAL of EcNAL</b></font> ([[1nal]]) (yellow), suggesting that this protein can perform either of these functions. Although the active site of EcDHDPS ([[1xky]]) and BaDHDPS ([[2ats]]) shows similarities, the important residue that differentiates between NAL and DHDPS, namely Leu142 (in [[1nal]]), is also present in YagE <scene name='2v9d/Leucine150/2'>(Leu150)</scene> <font color='cyan'><b>(labeled cyan)</b></font> at that particular position suggesting that YagE performs a NAL-related function rather than DHDPS-related one. In conclusion, the high-resolution X-ray structure of YagE provides a clue that it probably belongs to the NAL subfamily of proteins. Although the exact molecular function of YagE is still unknown, its structure provides a handle for understanding its molecular function based on knowledge about conserved residues of the putative active site.  
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</StructureSection>
==3D structures of dihydrodipicolinate synthase==


</StructureSection>
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*Dihydrodipicolinate synthase or 4-hydroxy-tetrahydrodipicolinate synthase
 
**[[4dpp]], [[6vvi]] – AtDPS – ''Arabidopsis thaliana''<br />
**[[3tuu]] – grDPS – grapevine<br />
**[[1dhp]], [[1s5t]], [[1s5v]], [[1s5w]], [[2a6l]], [[2a6n]], [[2ojp]], [[2pur]], [[3den]], [[3i7q]], [[3i7r]], [[7jz7]] – EcDPS (mutant) – ''Escherichia coli''<br />
**[[1yxc]] - EcDPS<br />
**[[1o5k]] – TmDPS – ''Thermotoga maritima''<br />
**[[3pb0]], [[3pb2]] – TmDPS (mutant)<br />
**[[1xky]], [[1xl9]] – BaDPS – ''Bacillus anthracis''<br />
**[[1xxx]] – MtDPS – ''Mycobacterium tuberculosis''<br />
**[[3l21]] – MtDPS (mutant)<br />
**[[2hmc]], [[2r8w]], [[3b4u]], [[4i7u]], [[4i7v]] – DPS – ''Agrobacterium tumdefaciens''<br />
**[[2ehh]] – DPS – ''Aquifex aeolicus''<br />
**[[2rfg]] – DPS – ''Hahella chejuensis''<br />
**[[2yxg]] – DPS – ''Methanocaldococcus jannaschii''<br />
**[[3d0c]] – DPS – ''Oceanobacillus iheyensis''<br />
**[[3daq]], [[3di0]] – SaDPS – ''Staphylococcus aureus''<br />
**[[3dz1]] – DPS – ''Rhodopseudomonas palustris''<br />
**[[3e96]] – DPS – ''Bacillus clausii''<br />
**[[3cpr]] – DPS – ''Corynebacterium glutamicum''<br />
**[[3g0s]] – DPS – ''Salmonella typhimurium''<br />
**[[3flu]] – DPS – ''Neisseria meningitides''<br />
**[[3ird]], [[3a5f]] – DPS – ''Clostridium botulinum''<br />
**[[3vfl]] – SpDPS – ''Streptococcus pneumoniae''<br />
**[[3ler]], [[3m5v]] – DPS – ''Campylobacter jejuni''<br />
**[[3noe]], [[3ps7]], [[3qze]] – PaDPS – ''Psuedomonas aeruginosa''<br />
**[[6p90]] - PaDPS (mutant) <br />
**[[3pud]], [[3pul]], [[4dxv]] – AbDPS – ''Acinetobacter baumannii''<br />
**[[3si9]] – DSP – ''Bartonella henselae''<br />
**[[4icn]] - SbDPS – ''Shewanella benthica''<br />
**[[4xky]] - DPS – ''Bacterioides thetaiotaomicron''<br />
**[[5czj]] - SmDPS – ''Sinorhizobium meliloti''<br />
**[[5ui3]] - DPS – ''Chlamydomonas reinhardtii''<br />
**[[7loy]] - ClDPS – ''Candidatus liberibacter''<br />
**[[6ue0]] - DPS – ''Klebsiella pneumoniae''<br />
**[[5ktl]] - DPS – ''Trichormus variabilis''<br />
**[[4r53]] - CjDPS – ''Campylobacter jejuni''<br />
 
*DHDPS binary  complexes
 
**[[4dpq]] - AtDPS + S-Lys<br />
**[[4i7w]], [[6vvh]] - AtDPS + Lys<br />
**[[7mds]] - AtDPS + inhibitor<br />
**[[4hnn]] - grDPS + Lys<br />
**[[5ud6]] - DPS + Lys – red alga<br />
**[[3pue]] - AbDPS + Lys<br />
**[[3tce]] - AbDPS + hydroxylysine<br />
**[[3tdf]] - AbDPS + ketobutanoic acid<br />
**[[3u8g]] - AbDPS + oxalic acid<br />
**[[3uqn]] - AbDPS + oxamic acid<br />
**[[3rk8]], [[3tak]] - AbDPS + pyruvate<br />
**[[3puo]] - PaDPS + Lys<br />
**[[3s8h]] - PaDPS + hydroxypropanoic acid<br />
**[[4fha]] - SpDPS + Lys<br />
**[[2vc6]] – SmDPS + pyruvate <br />
**[[4ly8]], [[4mlj]], [[7kwn]], [[7l4b]] - CjDPS + pyruvate <br />
**[[6tzu]], [[6u01]], [[7kel]], [[7kg5]], [[7klq]], [[7klt]], [[7kn2]], [[7ko1]], [[7koc]], [[7kr8]], [[7ku6]], [[7kx1]], [[7lbd]] - CjDPS (mutant) + pyruvate <br />
**[[7m06]] - CjDPS (mutant) + Lys derivative<br />
**[[5f1u]], [[5f1v]] - CjDPS + inhibitor<br />
**[[4mlr]] - CjDPS + pyruvate + Lys<br />
**[[3di1]] - SaDPS + pyruvate<br />
**[[1yxd]], [[2ats]] – EcDPS + S-Lys<br />
**[[3c0j]] - EcDPS + hydroxypyruvate<br />
**[[3du0]], [[7jzf]] - EcDPS + pyruvate<br />
**[[3i7s]] - EcDPS (mutant) + pyruvate<br />
**[[4eou]] - EcDPS + succinic semialdehyde<br />
**[[6nva]] - EcDPS + propionate<br />
**[[5t25]], [[5t26]] - EcDPS + inhibitor<br />
**[[3hij]] - BaDPS + pyruvate<br />
**[[6xgs]] - DPS + citrate – ''Brucella suis''<br />
**[[7lvl]] - ClDPS + S-Lys <br />
**[[4nq1]] - DPS + pyruvate – ''Legionella pneumophila''<br />
**[[6ue0]] - DPS + pyruvate – ''Klebsiella pneumoniae''<br />
**[[5j5d]] - MtDPS + ketopimelic acid<br />
 
*DHDPS ternary complexes
 
**[[4pfm]] - SbDPS + Lys + pyruvate<br />
**[[7kg2]] - CjDPS (mutant) + pyruvate + His<br />
**[[7kxh]], [[7lcf]], [[7kwp]] – CjDPS + pyruvate + Lys derivative<br />
**[[7kg9]], [[7kh4]], [[7kk1]], [[7kkd]], [[7kkg]], [[7kkt]], [[7kls]], [[7kly]], [[7km0]], [[7km1]], [[7kn9]], [[7knz]], [[7kpc]], [[7kpe]], [[7ko3]], [[7kr7]], [[7kto]], [[7kuz]], [[7kwf]], [[7kz2]] - CjDPS (mutant) + pyruvate + Lys derivative<br />
**[[4m19]], [[4mlr]] - CjDPS + pyruvate + Lys<br />
**[[7kxg]] - CjDPS + pyruvate + His<br />
**[[7jzc]], [[7jzg]] - EcDPS (mutant) + Lys + pyruvate<br />
**[[7jz9]], [[7jzb]] - EcDPS (mutant) + pyruvate + succinic semialdehyde <br />
**[[7jza]] - EcDPS (mutant) + pyruvate + Lys + succinic semialdehyde <br />
**[[7mjf]] - ClDPS + pyruvate + succinic semialdehyde <br />
}}
==Reference==
==Reference==
Crystal structure of YagE, a putative DHDPS-like protein from Escherichia coli K12., Manicka S, Peleg Y, Unger T, Albeck S, Dym O, Greenblatt HM, Bourenkov G, Lamzin V, Krishnaswamy S, Sussman JL, Proteins. 2008 Jun;71(4):2102-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18361457 18361457 ]
Crystal structure of YagE, a putative DHDPS-like protein from Escherichia coli K12., Manicka S, Peleg Y, Unger T, Albeck S, Dym O, Greenblatt HM, Bourenkov G, Lamzin V, Krishnaswamy S, Sussman JL, Proteins. 2008 Jun;71(4):2102-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18361457 18361457 ]

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Alexander Berchansky, Michal Harel