Principal Investigator:
Changjian Feng, PhD
Professor
Pharmaceutical Sciences
cfeng@salud.unm.edu
Curriculum Vitae
Phone: (505) 925-4326
Fax: (505) 925-4549
Lab Physical Address
2705 Frontier Ave Suite 220
Lab Mailing Address
Department of Pharmaceutical Sciences
MSC09 5360
1 University of New Mexico
Albuquerque, NM 87131-0001
Dr. Feng is an expert in biochemistry and biophysics of metalloproteins, with an emphasis on structural-dynamics-functional relationship. He has authored > 90 scientific manuscripts. He is an active reviewer for NIH and NSF, and also serves as referee for AHA, French National Research Agency, and Italian Ministry of Health.
Questions under investigation in Feng laboratory lie at the intersection of physics, chemistry and biology, with a particular emphasis on the molecular biophysics of oxidoreductase enzymes. Oxidoreductases consist of a large class of enzymes facilitating the transfer of electrons from an electron donor to an electron acceptor. Electron transfer in biology drives the processes of living systems. From cellular respiration to photosynthesis, metabolism and molecular signaling, electron transfers are chemical processes on which essential biological functions rely. Electron transfer within and between proteins is thus a fundamental biological process of great importance to living organisms. Protein are dynamic molecules. We focus on the central question: how Nature has optimized protein dynamics to promote electron transfer. This question forms his life work and is a source of endless fascination for him.
His primary research focus is on regulation mechanism of nitric oxide synthase (NOS), a flavo-hemoprotein responsible for biosynthesis of nitric oxide (NO), a ubiquitous signaling and effector molecule in mammalian cell biology. A particular strength is the utilization of multidisciplinary approaches, using advanced techniques ranging from biochemical, rapid kinetics, spectroscopic to genetic code expansion, to answer specific mechanistic questions. He has devoted particular effort to collaborative investigations of modular redox enzymes. Using quantitative tools integral to physics and chemistry, they aim to develop a collective knowledge in multidomain proteins by applying novel biophysical and computational tools to search for fundamental principles underlying the many reactions catalyzed by these enzymes. Recent studies of NOS proteins by Dr. Feng demonstrate that domain motions and interdomain docking play an important role in NOS isoform function by modulating key electron transfer processes. Molecular mechanisms of NOS regulation, once fully understood, are potentially key targets for development of selective new pharmaceuticals for treating a wide range of diseases that currently lack effective treatments.
Astashkin, Andrei V.; Li, Jinghui; Zheng, Huayu; Feng, Changjian*. (2019) Positional distributions of the tethered modules in nitric oxide synthase: Monte Carlo calculations and pulsed EPR measurements. J. Phys. Chem. A 123, 7075-7086.
Li, Jinghui; Zheng, Huayu; Feng, Changjian*. (2019) Effect of macromolecular crowding on the FMN - heme intraprotein electron transfer in inducible NO synthase. Biochemistry, 58, 3087-3096.
Zheng, Huayu; He, Jingxuan; Li, Jinghui; Yang, Jing; Kirk, Martin L.; Roman, Linda J.; Feng, Changjian*. (2019) Generation and characterization of functional phosphoserine incorporated neuronal nitric oxide synthase holoenzyme. J. Biol. Inorg. Chem. 24, 1-9.
Li, Jinghui; Zheng, Huayu; Wang, Wei; Miao, Yubin; Sheng, Yinghong; Feng, Changjian*. (2018) Role of an isoform-specific residue at the calmodulin-heme(NO synthase) interface in the FMN - heme electron transfer. FEBS Lett. 592, 2425-2431.
Astashkin, Andrei V.; Li, Jinghui; Zheng, Huayu; Miao, Yubin; Feng, Changjian*. (2018) A docked state conformational dynamics model to explain the ionic strength dependence of FMN-heme electron transfer in nitric oxide synthase. J. Inorg. Biochem. 184, 146-155.
Sheng, Yinghong; Zhong, Linghao; Guo, Dahai; Lau, Gavin; Feng, Changjian*. (2015) Insight into structural rearrangements and interdomain interactions related to electron transfer between flavin mononucleotide and heme in nitric oxide synthase: A molecular dynamics study, J. Inorg. Biochem.153, 186-196.
Astashkin, Andrei; Feng, Changjian*. (2015) Solving kinetic equations for the laser flash photolysis experiment on nitric oxide synthases: Effect of conformational dynamics on the interdomain electron transfer. J. Phys. Chem. A 119, 11066-11075.
Astashkin, Andrei; Chen, Li; Elmore, Bradley; Kunwar, Deepak; Miao, Yubin; Li, Huiying; Poulos, Thomas; Roman, Linda; Feng, Changjian*. (2015) Probing the hydrogen bonding of the ferrous−NO heme center of nNOS by pulsed electron paramagnetic resonance, J. Phys. Chem. A 119, 6641-6649.
Astashkin, Andrei; Chen, Li; Zhou, Xixi; Li, Huiying; Poulos, Thomas; Liu, Ke Jian; Guillemette, Joseph; Feng, Changjian*. (2014) Pulsed electron paramagnetic resonance study of domain docking in neuronal nitric oxide synthase: The calmodulin and output state perspective, J. Phys. Chem. A 118, 6864-6872.
Panda, Satya P.; Li, Wenbing; Venkatakrishnan, Priya; Chen, Li; Astashkin, Andrei. V.; Masters, Bettie Sue; Feng, Changjian; Roman, Linda J. (2013) Differential calmodulin-modulatory and electron transfer properties of neuronal nitric oxide synthase mu compared to the alpha variant, FEBS Lett. 587, 3973-3978.
Li, Wenbing; Chen, Li; Lu, Changyuan; Elmore, Bradley O.; Astashkin, Andrei V.; Rousseau, Denis L.; Yeh, Syun-Ru; Feng, Changjian*. (2013) Regulatory role of Glu546 in flavin mononucleotide - heme electron transfer in human inducible nitric oxide synthase, Inorg. Chem.52, 4795-4801.
Feng, Changjian*. (2012) Mechanism of nitric oxide synthase regulation: Electron transfer and interdomain interactions, Coord. Chem. Rev. 256, 393-411.
Astashkin, Andrei V.; Elmore, Bradley O.; Fan, Weihong; Guillemette, J. Guy.; Feng, Changjian*. (2010) Pulsed EPR determination of the distance between heme iron and FMN centers in a human inducible nitric oxide synthase, J. Am. Chem. Soc. 132, 12059-12067.
Sempombe, Joseph; Elmore, Bradley; Sun, Xi; Dupont, Andrea; Ghosh, Dipak; Guillemette, Joseph; Kirk, Martin; Feng, Changjian*. (2009) Mutations in the FMN domain modulate MCD spectra of the heme site in the oxygenase domain of inducible nitric oxide synthase, J. Am. Chem. Soc. 131, 6940-6941.
Feng, Changjian*; Tollin, Gordon; Hazzard, James T.; Nahm, Nickolas J.; Guillemette J. Guy; Salerno, John C.; Ghosh, Dipak K. (2007) Direct measurement by laser flash photolysis of intraprotein electron transfer in a rat neuronal nitric oxide synthase, J. Am. Chem. Soc.129, 5621-5629.
Feng, Changjian*; Tollin, Gordon; Holliday, Michael A.; Thomas, Clayton; Salerno, John C.; Enemark, John H.; Ghosh, Dipak K. (2006) Intraprotein electron transfer in a two-domain construct of neuronal nitric oxide synthase: The output state in nitric oxide formation, Biochemistry45, 6354-6362.
Feng, Changjian; Thomas, Clayton; Holliday, Michael A.; Tollin, Gordon; Salerno, John C.; Ghosh, Dipak K.; Enemark John H. (2006) Direct measurement by laser flash photolysis of intramolecular electron transfer in a two-domain construct of murine inducible nitric oxide synthase, J. Am. Chem. Soc. 128, 3808-3811.
