5th5

Crystal Structure of QueE from Bacillus subtilis with 6-carboxypterin-5'-deoxyadenosyl ester boundCrystal Structure of QueE from Bacillus subtilis with 6-carboxypterin-5'-deoxyadenosyl ester bound

Structural highlights

5th5 is a 4 chain structure with sequence from Bacillus subtilis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.407Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

QUEE_BACSU Catalyzes the complex heterocyclic radical-mediated conversion of 6-carboxy-5,6,7,8-tetrahydropterin (CPH4) to 7-carboxy-7-deazaguanine (CDG), a step common to the biosynthetic pathways of all 7-deazapurine-containing compounds.[HAMAP-Rule:MF_00917]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Radical S-adenosyl-L-methionine (SAM) enzymes are widely distributed and catalyze diverse reactions. SAM binds to the unique iron atom of a site-differentiated [4Fe-4S] cluster and is reductively cleaved to generate a 5-deoxyadenosyl radical, which initiates turnover. 7-Carboxy-7-deazaguanine (CDG) synthase catalyzes a key step in the biosynthesis of 7-deazapurine containing natural products. 6-Carboxypterin (6-CP), an oxidized analog of the natural substrate 6-carboxy-5,6,7,8-tetrahydropterin (CPH4), is shown to be an alternate substrate for CDG synthase. Under reducing conditions that would promote the reductive cleavage of SAM, 6-CP is turned over to 6-deoxyadenosylpterin, presumably by radical addition of the 5-deoxyadenosine followed by oxidative decarboxylation to the product. By contrast, in the absence of the strong reductant, dithionite, the carboxylate of 6-CP is esterified to generate 6-carboxypterin-5-deoxyadenosyl ester. Structural studies with 6-CP and SAM also reveal electron density consistent with the ester product being formed in crystallo. The differential reactivity of 6-CP under reducing and non-reducing conditions highlights the ability of radical SAM enzymes to carry out both polar and radical transformations in the same active site. .

7-Carboxy-7-deazaguanine synthase - A radical S-adenosyl-L-methionine enzyme with polar tendencies.,Bruender NA, Grell TA, Dowling DP, McCarty RM, Drennan CL, Bandarian V J Am Chem Soc. 2017 Jan 3. doi: 10.1021/jacs.6b11381. PMID:28045519^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Reader JS, Metzgar D, Schimmel P, de Crecy-Lagard V. Identification of four genes necessary for biosynthesis of the modified nucleoside queuosine. J Biol Chem. 2004 Feb 20;279(8):6280-5. Epub 2003 Dec 2. PMID:14660578 doi:http://dx.doi.org/10.1074/jbc.M310858200
↑ McCarty RM, Somogyi A, Lin G, Jacobsen NE, Bandarian V. The deazapurine biosynthetic pathway revealed: in vitro enzymatic synthesis of PreQ(0) from guanosine 5'-triphosphate in four steps. Biochemistry. 2009 May 12;48(18):3847-52. doi: 10.1021/bi900400e. PMID:19354300 doi:http://dx.doi.org/10.1021/bi900400e
↑ McCarty RM, Krebs C, Bandarian V. Spectroscopic, steady-state kinetic, and mechanistic characterization of the radical SAM enzyme QueE, which catalyzes a complex cyclization reaction in the biosynthesis of 7-deazapurines. Biochemistry. 2013 Jan 8;52(1):188-98. doi: 10.1021/bi301156w. Epub 2012 Dec 24. PMID:23194065 doi:http://dx.doi.org/10.1021/bi301156w
↑ Bruender NA, Grell TA, Dowling DP, McCarty RM, Drennan CL, Bandarian V. 7-Carboxy-7-deazaguanine synthase - A radical S-adenosyl-L-methionine enzyme with polar tendencies. J Am Chem Soc. 2017 Jan 3. doi: 10.1021/jacs.6b11381. PMID:28045519 doi:http://dx.doi.org/10.1021/jacs.6b11381

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OCA

[1] Reader JS, Metzgar D, Schimmel P, de Crecy-Lagard V. Identification of four genes necessary for biosynthesis of the modified nucleoside queuosine. J Biol Chem. 2004 Feb 20;279(8):6280-5. Epub 2003 Dec 2. PMID:14660578 doi:http://dx.doi.org/10.1074/jbc.M310858200

[2] McCarty RM, Somogyi A, Lin G, Jacobsen NE, Bandarian V. The deazapurine biosynthetic pathway revealed: in vitro enzymatic synthesis of PreQ(0) from guanosine 5'-triphosphate in four steps. Biochemistry. 2009 May 12;48(18):3847-52. doi: 10.1021/bi900400e. PMID:19354300 doi:http://dx.doi.org/10.1021/bi900400e

[3] McCarty RM, Krebs C, Bandarian V. Spectroscopic, steady-state kinetic, and mechanistic characterization of the radical SAM enzyme QueE, which catalyzes a complex cyclization reaction in the biosynthesis of 7-deazapurines. Biochemistry. 2013 Jan 8;52(1):188-98. doi: 10.1021/bi301156w. Epub 2012 Dec 24. PMID:23194065 doi:http://dx.doi.org/10.1021/bi301156w

[4] Bruender NA, Grell TA, Dowling DP, McCarty RM, Drennan CL, Bandarian V. 7-Carboxy-7-deazaguanine synthase - A radical S-adenosyl-L-methionine enzyme with polar tendencies. J Am Chem Soc. 2017 Jan 3. doi: 10.1021/jacs.6b11381. PMID:28045519 doi:http://dx.doi.org/10.1021/jacs.6b11381

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