Steve Ealick's Research Group

Yang Zhang


PhD: Cornell Univeristy, 2005, Biochemistry


X-ray Crystallographic and Mechanistic Studies of Three Enzymes

Current Projects:

Structural studies of enzymes involved in the Rut pathway for pyrimidine degradation, in diphthamide biosynthesis, and in PLP biosynthesis, as well as further studies on Toxoplasma adenosine kinase.


Mori S, Simkhada D, Zhang H, Erb MS, Zhang Y, Williams HJ, Fedoseyenko D, Russell WK, Kim D, Fleer N, Ealick SE, and Watanabe CM. Polyketide Ring Expansion Mediated by a Thioesterase, CEC Domain, in Azinomycin Biosynthesis: Characterization of AziB and AziG. Biochemistry 55:704-714 (2016). PubMed.

Mehta AP, Abdelwahed SH, Fenwick MK, Hazra AB, Taga ME, Zhang Y, Ealick SE, and Begley TP. Anaerobic 5-Hydroxybenzimidazole formation from aminoimidazole ribotide: an unanticipated intersection of thiamin and vitamin B12 biosynthesis. J. Am. Chem. Soc.137:10444−10447 (2015). PubMed

Li B, Kim SH, Zhang Y, Hanfrey CC, Elliott KA, Ealick SE, and Michael AJ. Different polyamine pathways from bacteria have replaced eukaryotic spermidine biosynthesis in ciliates Tetrahymena thermophila and Paramecium tetaurelia. Mol. Microbiol. 97:791-807 (2015). PubMed

Fenwick MK, Mehta AP, Zhang Y, Abdelwahed SH, Begley TP, and Ealick SE. Noncanonical Active Site Architecture of the Radical SAM Thiamin Pyrimidine Synthase. Nat. Commun. 6:6480 (2015). PubMed (AtThiC and CcThiC)

Sikowitz MD, Shome B, Zhang Y, Begley TP, and Ealick SE. Structure of a Clostridium botulinum C143S thiaminase I/thiamin complex reveals active site architecture. Biochemistry 52:7830−7839 (2013). PubMed

Soriano EV, Zhang Y, Colabroy K, Sanders JM, Settembre EC, Dorrestein PC, Begley TP, and Ealick SE. Active Site Models for Complexes of Quinolinate Synthase with Substrates and Intermediates. Acta Crystallogr. D. 69:1685–1696 (2013). PubMed

Lai RY, Huang S, Fenwick MK, Hazra AB, Zhang Y, Rajashankar KR, Philmus B, Kinsland C, Sanders JM, Ealick SE, and Begley TP. Thiamin pyrimidine biosynthesis in Candida albicans: a remarkable reaction between histidine and pyridoxal phosphate. J. Am. Chem. Soc. 134:9157−9159. (2012). PubMed

Dessanti P, Zhang Y, Allegrini S, Tozzi MG, Sgarrella F, and Ealick SE. Structural basis of the substrate specificity of Bacillus cereus adenosine phosphorylase. Acta Crystallogr. D 68:239-248 (2012). PubMed

Zhang Y, Zwart PH, and Ealick SE. A corrected space group for Sulfolobus sulfataricus 5'-deoxy-5'-methylthioadenosine phosphorylase II. Acta Crystallogr. D 68:249-252 (2012). PubMed

Hazra AB, Han Y, Chatterjee A, Zhang Y, Lai RY, Ealick SE, and Begley TP. A Missing Enzyme in Thiamin Thiazole Biosynthesis: Identification of TenI as a Thiazole Tautomerase. J. Am. Chem. Soc.133:9311-9319 (2011). PubMed

Zhu X, Dzikovski B, Su X, Torelli AT, Zhang Y, Ealick SE, Freed JH, and Lin H. Mechanistic Understanding of Pyrococcus horikoshii Dph2, a [4Fe-4S] Enzyme Required for Diphthamide Biosynthesis. Mol. Biosyst. 7:74-81 (2011). PubMed

Zhang Y, Zhu X, Torelli AT, Lee M, Dzikovski B, Koralewski RM, Wang E, Freed J, Krebs C, Ealick SE, and Lin H. Diphthamide biosynthesis requires an organic radical generated by an iron–sulphur enzyme. Nature 465:891-896 (2010). PubMed; associated Nature News and View article. Associated article in Chemical & Engineering News. Nature Chemical Biology recently described this radical new SAM mechanism as one of the key developments in chemical biology in the past decade.

Mukherjee T, Zhang Y, Abdelwahed S, Wemmer D, Ealick SE, and Begley TP. Catalysis of a Flavoenzyme-Mediated Amide Hydrolysis. J. Am. Chem. Soc. 132:1550-1551 (2010). PubMed

Kang YN, Zhang Y, Allan PW, Parker WB, Ting JW, Chang CY and Ealick SE. Crystal Structure of Grouper Iridovirus Purine Nucleoside Phosphorylase. Acta Crystallogr. D 66:155-162 (2010).PubMed. PDF version by permission of the publisher.

Chatterjee A, Li Y, Zhang Y, Grove TL, Lee M, Krebs C, Booker SJ, Begley TP, and Ealick SE. Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily. Nat. Chem. Biol. 4, 758-765. PubMed

Zhang Y, Morar M and Ealick SE. Structural biology of the purine biosynthetic pathway. Cell. Mol. Life Sci.65:3699-3724 (2008). Abstract. PubMed

Zhang Y, White RH and Ealick SE. Crystal Structure and Function of 5-Formaminoimidazole-4-Carboxamide Ribonucleotide Synthetase from Methanocaldococcus jannaschii. Biochemistry 47:205-217 (2008).PubMed. (Also includes the structure of the homologous enzyme, as yet functionally uncharacterized, from Pyrococcus furiosus, PfPurP.)

Jenkins AL, Zhang Y, Ealick SE and Begley TP. Mutagenesis studies on TenA: A thiamin salvage enzyme from Bacillus subtilis. Bioorg. Chem. 36:29-32 (2008). PubMed.

Zhang Y and Ealick SE. Purine Nucleoside Phosphorylase in "Computational and Structural Approaches to Drug Discovery Ligand-Protein Interactions", Stroud RM and Finer-Moore J, eds., Royal Society of Chemistry, London (2007). ISBN 0854043659.

Zhang Y, Kang SA, Mukherjee T, Bale S, Crane BR, Begley TP and Ealick SE. Crystal Structure and Mechanism of Tryptophan 2,3-Dioxygenase, a Heme Enzyme Involved in Tryptophan Catabolism and in Quinolinate Biosynthesis. Biochemistry 46:145-155 (2007). PubMed

Zhang Y, Parker WB, Sorscher EJ, and Ealick SE. PNP Anticancer Gene Therapy, Curr. Top. Med. Chem. 5:1259-1274 (2005). PubMed

Zhang Y, Wang W-H, Wu S-W, Ealick SE, and Wang CC. Identification of the Subversive Substrate of Trichomonas vaginalis Purine Nucleoside Phosphorylase and the Crystal Structure of the Enzyme-Substrate Complex. J. Biol. Chem. 280:22318-22325 (2005). PubMed

Zhang Y, Colabroy KL, Begley TP, and Ealick SE. Structural studies on 3-hydroxyanthranilate-3,4-dioxygenase: the catalytic mechanism of a complex oxidation involved in NAD biosynthesis. Biochemistry. 44:7632-7643 (2005). PubMed

Dontsova MV, Gabdoulkhakov AG, Molchan OK, Lashkov AA, Garber MB, Mironov AS, Zhukhlistova NE, Morgunova EYu, Voelter,W, Betzel C, Zhang Y, Ealick SE and Mikhailov AM. Preliminary Investigation of the Three-dimensional Structure of Salmonella typhimurium Uridine Phosphorylase in the Crystal State. Acta Crystallogr. F. 61:337-340 (2005). PubMed

Colabroy KL, Zhai H, Li T, Ying Ge1, Zhang Y, Liu A, Ealick SE, McLafferty FW and Begley TP, The mechanism of inactivation of 3-hydroxyanthranilate-3,4-dioxygenase by 4-chloro-3-hydroxyanthranilate. Biochemistry 44:7623-7631 (2005). PubMed

Zhang Y, Cottet SE and Ealick SE. Structure of E. coli AMP Nucleosidase Reveals Similarity to Nucleoside Phosphorylases. Structure 12: 1383-94 (2004). PubMed

Tolbert WD, Zhang Y, Cottet SE, Bennett EM, Ekstrom JL, Pegg AE and Ealick SE. Mechanism of Human S-Adenosylmethionine Decarboxylase Proenzyme Processing as Revealed by the Structure of the S68A Mutant. Biochemistry 42:2386-2395 (2003). PubMed

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